Host Genetic Determinants of the Vaginal Microbiome in Kenyan Women

Host Genetic Determinants of the Vaginal Microbiome in Kenyan Women | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Host Genetic Determinants of the Vaginal Microbiome in Kenyan Women Supriya D Mehta, Drew R Nannini, Fredrick Otieno, Stefan J. Green, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-17153/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Women with vaginal microbial community state types (CST) with high diversity and a paucity of Lactobacillus crispatus have increased risk of HIV acquisition. Identifying host genetic factors associated with the vaginal microbial composition may aid in elucidating the biological mechanisms regulating these microbial traits and inter-individual variations in associated diseases. Methods We conducted genome-wide associations studies (GWASs) on vaginal microbiome traits on 171 Kenyan women. Study participants were genotyped using the Infinium Global Screening Array and 16S rRNA gene amplicon sequencing was performed to characterize the vaginal microbiome. Linear and logistic regression were performed, adjusting for age and principal components of genetic ancestry, to evaluate the association between L. crispatus, L. iners, G. vaginalis, Shannon diversity index, and CST with host genetic single nucleotide polymorphisms (SNPs). Pathway enrichment analyses were performed to identify biological processes putatively associated with the vaginal microbiome traits. Results At baseline, the median age of study participants was 22 years (IQR: 22 – 25) with 22% having Bacterial vaginosis (Nugent score 7-10). L. crispatus and L. iners were present in 24% and 83% of samples with a mean relative abundance of 31% and 45%, respectively. The most significant SNPs associated were: rs73330467 located between LOC101927488-GRAMD2B ( P =4.79x10 -6 ) for L. crispatus ; rs527430 in the FOXD2-TRABD2B ( P =6.98x10 -7 ) region for L. iners ; rs1229660 in the SNX10-LOC441204 ( P =4.65x10 -6 ) region for G. vaginalis; rs972741 in the ZKSCAN2-HS3ST4 ( P =8.52x10 -7 ) region for Shannon diversity index; and rs2302902 in ELK3 ( P =3.09x10 -6 ) for CST. During pathway enrichment analysis, Toll-like receptors, cytokine production, and other components of innate immune response were associated with L. crispatus, L. iners, and CST. Multiple genomic loci were replicated, including IL-8 (Shannon, CST), TIRAP ( L. iners , Shannon), TLR2 (Shannon, CST), MBL2 ( L. iners , G. vaginalis , CST), and MYD88 ( L. iners, Shannon). Conclusions We identified numerous genetic loci on several pathways related to host immunity and infection that were associated with vaginal microbiome traits, providing insight into potential host genetic influences on vaginal microbiome composition. This new information should guide larger longitudinal studies, with genetic and functional comparison across microbiome sites within individuals, and across populations. General Microbiology Vaginal microbiome Vaginal microbiota Bacterial vaginosis L. crispatus L. iners G. vaginalis Shannon diversity index community state type genome wide association study pathway analysis toll-like receptors innate immune response Kenya Figures Figure 1 Figure 2 Figure 3 Introduction Bacterial vaginosis (BV) is a condition of clinical and public health significance. BV is prevalent in 20–50% of women in sub-Saharan Africa [ 1 ]. In a meta-analysis, Atashili et al. estimated the relative risk of HIV acquisition to be 1.6 times higher for women with BV, equating to a population attributable fraction of 15% due to the high population prevalence [ 2 ]. BV is also associated with an increased likelihood of sexually transmitted infections (STI) and adverse pregnancy outcomes [ 3 , 4 ]. BV represents a polymicrobial shift in the vaginal microbiome, often from a Lactobacillus dominant community to one that is diverse, with multiple species of anaerobic bacteria [ 5 ]. In particular, L. crispatus enrichment has been shown to be protective against BV, HIV, and STIs [ 6 ]. BV is considered a sexually enhanced infection, and individuals with new or multiple sex partners, those who engage in unprotected vaginal sex, or those whose sex partner is uncircumcised are at an increased risk of BV [ 3 , 7 – 9 ]. In addition to sexual risk factors, non-sexual risk factors that are associated with BV include intravaginal and vaginal hygiene practices [ 10 ], cigarette smoking [ 11 ], and race/ethnicity [ 12 ]. In numerous studies, women of African descent have increased risk of BV and non-optimal vaginal microbiome composition [ 13 ]. These associations with race persist even when controlling for socio-demographics and sexual practices [ 14 , 15 ], leading to the hypothesis that genetic factors may influence the vaginal microbiome composition and subsequently BV [ 16 ]. To date, a limited number of studies have examined the host genetic contribution to the vaginal flora and BV. Primarily these studies have focused on host differences in candidate genes responsible for inflammatory mucosal immune response in other infectious conditions [ 16 , 17 ]. As reviewed by Turovskiy et al., studies have targeted single nucleotide polymorphisms (SNPs) in: (1) Toll-like receptor (TLR) genes because of their role in recognizing potential threats and initiating inflammatory responses and activating other immune cells, and (2) pro-inflammatory and inflammatory cytokines (e.g., IL-1β, TNF-α) [ 15 ]. Most of these studies, however, evaluated SNPs in relation to BV or to specific taxa associated with BV (e.g., G. vaginalis , A. vaginae spp.) and none of the studies measured the vaginal microflora or host genetic contribution comprehensively, such as with cultivation-independent molecular microbial characterization or a genome wide association study (GWAS), respectively. To address this gap, we conducted GWAS on vaginal microbiome traits among native Kenyan women. We hypothesized that by conducting GWAS, we would identify novel genomic loci associated with vaginal microbiome traits, furthering our understanding of the underlying genetic factors. Identifying genetic variants may aid in elucidating the biological mechanisms associated with these complex vaginal microbiome traits and associated diseases. Complementary to GWAS, we conducted replication analyses of SNPs previously reported to be associated with vaginal microflora or BV. Results Study Sample Among 171 women included in this analysis, the prevalence of BV at baseline was 22% ( Table 1 ). Over half (53%) of women were HSV-2 seropositive and 10% were HIV positive, which is in keeping with the prevalence of HIV among women in this age range in the general population in this region of western Kenya [18]. L. crispatus was present in 25% of samples (28% mean relative abundance), L. iners was present in 83% of samples (mean relative abundance 45%), and G. vaginalis was present in 75% of samples (25% mean relative abundance). Genome-wide association results The genomic control (GC) inflation factor, l, was 1.01, 1.00, 1.00, 1.00, and 1.00 for L. crispatus , L. iners , G. vaginalis , the Shannon diversity index, and CST, respectively, after adjusting for age and the first three principal components. Upon visual inspection of the Q-Q plots ( Supplementary Figure 1 ), the observed P values do not deviate from the null, except at the extreme tail. Together with the genomic inflation factors, the Q-Q plots indicate proper control of population stratification. Figure 1A-E displays the Manhattan plots of the genome-wide P values for each vaginal microbiome trait. Table 2 summarizes the top SNPs ( P < 1 x 10 -5 ) for each vaginal microbiome trait and minor allele frequencies (MAF) derived from our data. Overall, no SNP reached genome-wide significance (0.05/336,151 = 1.49E-07). The SNP with the lowest adjusted p-value associated with presence of L. crispatus was rs73330467 ( P = 4.79 x 10 -6 , Figure 1A ), located in an intergenic region between LOC101927488 and GRAMD2B on chromosome 5. The minor allele G (MAF = 0.07) was associated with an 11.6-fold increased odds of detecting L. crispatus . The most significant SNP associated with relative abundance of L. iners was rs527430 ( P = 6.98 x 10 -7 , Figure 1B ) on chromosome 1, located in an intergenic region between FOXD2 and TRABD2B . The minor allele A (MAF = 0.06) was associated with an increase in relative abundance of L. iners (β = 1.05). The most significant SNP associated with G. vaginalis was rs1229660 ( P = 4.65 x 10 -6 , Figure 1C ) located between SNX10-LOC441204 on chromosome 7. The minor allele C (MAF = 0.10) was associated with a decrease in G. vaginalis relative abundance (β = -0.99). The most significant SNP associated with Shannon diversity index was rs972741 ( P = 8.52 x 10 -7 , Figures 1D ) located between ZKSCAN2 and HS3ST4 on chromosome 16. The minor allele A (MAF = 0.19) was associated with an increase in the Shannon diversity index (β= 0.66). The most significant SNP associated with CST was rs2302902 ( P = 3.09 x 10 -6 , Figure 1E ) located in ELK3 on chromosome 12. The minor allele T (MAF = 0.20) was associated with an increased likelihood of membership in lower diversity CST-I and CST-II as compared to CST-IV (β= 0.41). Results from Imputed SNPs We performed genotype imputation in order to expand genomic coverage and interrogate additional SNPs not directly genotyped. After removing SNPs with low imputation quality and low frequency (Rsq < 0.30 and MAF < 1%), several imputed SNPs (but no additional genomic regions) were identified. Figure 2 presents the regional SNP association plots for each of the vaginal microbiome traits. Within the ZKSCAN2-HS3ST4 intergenic region on chromosome 16, several imputed SNPs were more significantly associated with the Shannon diversity index than those directly genotyped ( Figure 2E ). The most significant SNP in this region was rs115869045 ( P = 4.77 x 10 -7 , Rsq = 0.70). Conditional Analyses We conducted conditional analyses for the genomic loci in which the most significant SNP was identified for each vaginal microbiome trait to determine whether additional SNPs contribute to the observed associations. Supplementary Figure 2 displays the regional SNP associations conditioning on the most significant directly genotyped SNP by including the SNP as a covariate in the regression model. As shown in each plot, all of the immediate SNP associations reduced towards the null, suggesting the SNPs identified are the leading SNPs for the observed associations. Analysis of Previously Reported Loci We investigated the associations of previously reported SNPs in relation to BV or vaginal microflora to determine whether these associations are relevant in a Kenyan population. Figure 3 and Supplemental Table 1 summarize these findings. Overall, 49 autosomal SNPs were identified from previous studies, of which 45 SNPs exhibited high imputation quality (Rsq ³ 0.30). When analyzed, 7 SNPs for L. iners , 8 SNPs for L. crispatus , 6 SNPs for G. vaginalis , 10 SNPs for the Shannon Diversity Index, and 8 SNPs for CST had a P < 0.05 in our sample. These findings, however, were not significant after applying a Bonferroni correction (0.05 / 49 = 0.00102). To replicate genomic loci associated with the microbiome traits, we extracted the most significant imputed SNP within ± 100 kb of the previously reported SNPs for each microbiome trait in our study. This approach resulted in 6 genomic regions for L. iners , 1 genomic region for G. vaginalis , 7 genomic regions for Shannon Diversity Index, and 4 genomic regions for CST that were significant after Bonferroni correction ( Figure 3, Supplemental Table 1 ). No regions were significant after multiple testing correction for L. crispatus . The replicated genomic regions include IL1RN (CST), IL5 (Shannon), IL5RA ( L. iners, Shannon), IL-8 (Shannon, CST), TIRAP ( L. iners , Shannon), TLR2 (Shannon, CST), TLR3 ( L. iners, Shannon) , TLR4 ( L. iners ), MBL2 ( L. iners , G. vaginalis , CST), and MYD88 ( L. iners, Shannon). Pathway and Pleiotropy Analyses Table 3 presents the top five KEGG and Reactome pathways from WebGestalt for each vaginal microbiome trait. Four pathways were significantly associated with L. crispatus after Benjamini-Hochberg multiple testing adjustment, including G-protein-coupled receptor (GPCR) ligand binding and neutrophil degranulation. Five pathways were associated with L. iners : 4 related to TLR cascades, and one to the TLR upstream component (MyD88:Mal TIRAP; MyD88-adaptor-like TIR-domain containing adaptor protein). Two biological pathways related to GPCR signaling were associated with G. vaginalis , as well as ‘neutrophil degranulation’, though it did not meet Bonferroni significance. Similarly, two pathways were associated with CST, including the most significant pathway ‘Class B/2 (secretin family receptors)’, and one pathway was associated with the Shannon diversity index, ‘Class B/2 (secretin family receptors)’. Table 4 summarizes the top five DisGeNET, GLAD4U, OMIM, and Human Phenotype Ontology terms from WebGestalt for each vaginal microbiome trait. Five phenotypes were significantly associated with L. crispatus after Benjamini-Hochberg multiple testing adjustment, including ‘Bacterial infections’ ( P = 0.011) as the most significant phenotype. Three phenotypes were associated with L. iners , with ‘Autosomal dominant inheritance’ the most significant ( P = 0.018). No phenotypes were significantly associated with G. vaginalis . One phenotype was associated with the Shannon diversity index, ‘Abnormality of the female genitalia’ ( P = 0.037). Five phenotypes were associated with CST, including ‘Abnormality of the integument’ ( P = 0.00023). Discussion To our knowledge, this is the first GWAS of vaginal microbiome traits. In native Kenyan women, we identified novel genomic loci and biological pathways with biological relevance to host immunity, cell signaling, and infection, supporting the role of host genetics in inter-individual variability in vaginal microbiome traits. In GWAS, the most significant SNP associated with CST (rs2302902) is located in an intron of ELK3 , a member of the ETS transcription factor family, which has not been previously associated with any vaginal microbiome traits or BV. Proteins in the ELK3 subfamily are recruited by serum response factor and participate in transcription regulation, and has been associated in various cancers [ 19 – 21 ], including HPV-positive tumors of oropharyngeal cancer [ 22 ]and HPV16 in cervical tumors [ 23 ]. In meta-analysis, molecular and clinical measure of BV is associated with two-fold increase in risk of high-grade cervical epithelial neoplasia (CIN) or cancer [ 24 ]. Non-optimal vaginal microbiome leads to mucosal disruption and a pro-inflammatory environment that can facilitate HPV acquisition [ 25 ], but there may also be underlying shared or synergistic mechanism with ELK3. Other SNPs identified in GWAS occurred primarily in intergenic regions that haven’t previously been associated with BV or vaginal microbiome traits, and should be assessed for replication in future studies. BV was absent from CST-I ( L. crispatus dominant) and infrequent (5.1%) in CST-III. Although CST-IV accounted for 89% of BV cases in this sample, 57% of women in CST-IV did not have BV. This is in keeping with many other studies: women with diverse CSTs are much more likely to have BV, but as many as 50% of women with these CSTs do not have BV [ 26 ]. Host genetics may partially explain this variability. For example, women with similar vaginal bacterial colonization (such as those within CST-IV) may have different response to bacterial colonization depending on genetic traits. For women who mount an inflammatory response, this immune response may potentiate BV rather being solely a response to BV. In our study, restricting analyses to HIV uninfected women did not change our findings. This is not entirely unexpected, as associations between HIV and subsequent impact on the vaginal microbiome are variable, with some finding no effect [ 27 , 28 ]. Conversely, there is substantial data that demonstrate the temporal association between non-optimal vaginal microbiome composition, mucosal inflammation, and subsequent HIV risk [ 29 ], and our results suggest that host genetic differences may underpin this. Well-powered longitudinal studies that examine how host genetics is associated with varying CST, mucosal immune markers, and BV trajectories could be informative to understanding this variability in pathology within non-optimal CSTs. Additionally studies are needed to explore the potential long range regulation of these SNPs on genes, as well as evaluate for expression or methylation quantitative trait loci associations. Complex traits are polygenic, and our analysis of previously reported loci identified multiple SNPs across numerous genetic loci with Bonferroni corrected significance. Several SNPs in the MBL2 region were significantly associated with L. iners , G. vaginalis , and CST. Kalia et al. studied these previously reported MBL2 SNPs in association with BV in women in India due to associations between mannose binding lectin (MBL) insufficiency and increased susceptibility to infectious diseases [ 30 ]. Among Brazilian women, a specific MBL2 polymorphism was associated with increased odds of recurrent BV compared to controls [ 31 ], though a study among Italian women that screened for three specific MBL2 SNPs found no differences for women with recurrent BV as compared to controls [ 32 ]. The relevance of this gene may be population specific or subject to interaction with other factors such as the prevalence of co-infections (e.g., HSV-2, HIV), sexual exposures (e.g., partner circumcision status, multiple sex partners, condom use), or non-sexual factors (e.g., cigarette smoking, intravaginal practices). Additionally, we identified SNPs in IL-1RN (CST), IL-5 (Shannon), and IL5RA ( L. iners , Shannon). IL-1RN (the gene for interleukin 1 receptor agonist, IL-1RA) inhibits the inflammatory IL-1 cytokines, IL-1α, and IL-1β. In a study of 62 Italian women, compared to women with Nugent score 0–3, women with BV (Nugent score 7–10) had increased IL-1RA, and increased inflammatory IL-5 was associated with decreased Lactobacillus [ 33 ]. In candidate gene analysis, Si et al. targeted genetic variants of IL-5 finding association with increased abundances of various Prevotella [ 34 ]. Our findings further these studies by analyzing genetic factors and vaginal microbiome traits in a novel population and by demonstrating trans-ethnic associations for these previously identified loci. In pathway analysis, GPCR pathways were identified with L. crispatus , G. vaginalis , and CST, and Class B/2 (secretin family receptors) within the GPCR family were identified with Shannon diversity index and CST. GPCRs play a significant role in intracellular signaling in response to a broad range of stimuli (e.g., hormones, neurotransmitters, proteins, etc.) and across a wide range of functions (e.g., growth, nutrition requirements, response to disease, etc.) [ 35 ]. This likely includes vaginal microbiome modulation, and variation in GPCR signaling may related to variations in innate immune response. LL-37 is elevated in women with BV and in an ex vivo endocervical model, after application of a GPCR inhibitor, LL-37 mediated induction of IL-8 production was inhibited [ 36 ]; this is relevant given that IL-8 is often elevated in women with BV [ 37 ]. In analyses of previously reported SNPs, we found SNPs in the IL-8 gene region were associated with Shannon diversity index and CST. In an experimental study, Mares et al. demonstrate that application of CVL from women with BV induced higher levels of IL-8 and NFkappaB in human monocytes than CVL from women without BV [ 38 ]. Among women in the CAPRISA 004 trial, those with vaginal CST-IV had increased mucosal inflammation (including elevated IL-8) and increased risk of HIV seroconversion [ 29 ]. The effects of variation in GPCR signaling on innate immune response may extend to other outcomes. Among Dutch women, GWAS and pathway analysis found that genes encoding GPCR signaling were enriched for 71 Chlamydia trachomatis seropositive women compared to 169 control women [ 39 ]. GPCR signaling encompasses a broad range of actions, but in conjunction with our pathway results implicating IL-8 and TLRs, and other studies showing potential roles for GPCR in cervicovaginal health, GPCR signaling merits further study as a potential pathway affecting acquisition or maintenance of vaginal L. crispatus , CST membership, and subsequent BV status. Our pathway analysis additionally linked neutrophil degranulation with L. crispatus and G. vaginalis . Neutrophils are effector cells in innate immunity and degranulation can have serious adverse consequences for the host due to release of damaging molecules. We are unaware of other studies linking neutrophil degranulation to the vaginal microbiome, BV, or other vaginal infections. However, myeloperoxidase (MPO) is a measure of neutrophils and is elevated in women with sexually transmitted infection (STI) [ 40 ]. Whether neutrophil degranulation is an important process in vaginal microbiome composition may be evaluated in subsequent studies, such as by targeting genes encoding molecules associated with this pathway (e.g., β-arrestins, Rac2) [ 41 ]. Lastly, pathway analysis identified ‘MyD88:MAL (TIRAP) cascade’ with L. iners , and we identified SNPs within the MyD88 gene in relation to L. iners and Shannon diversity index. MyD88:Mal (TIRAP) is an adaptor to MyD88, the first downstream component of TLR4 and TLR2, and part of the larger overall process for inflammatory cytokine effects [ 42 ]. In pathway analysis, several TLR signaling associations were associated with L. iners relative abundance, and in analysis of previously reported SNPs, TLR2, and TLR3 had associations with Shannon diversity index, CST, and L. iners . As summarized in Supplementary Table 1, several investigators have found polymorphisms in TLR genes related to altered risk of BV and enrichment of BV-related bacteria. TLRs, especially TLR2 alone or in combination with TLR-1/TLR-6 and TLR-4, have been recognized for their association with BV and BV-related bacteria, as these TLRs precipitate release of pro-inflammatory cytokines and recruitment of inflammatory cells [ 43 – 47 ]. As summarized by Taylor et al., TLR gene variants can lead to inadequate or excess inflammatory immune response, which can affect disease susceptibility or progression [ 44 ]. Additionally studies are needed to evaluate the potential biological role TLRs have on vaginal microbiome composition. Given that the microbiome is a complex trait and complex traits are pleiotropic, this may provide understanding of how TLR variants contribute to risk of BV, response to BV treatment, or other outcomes of non-optimal vaginal microbiome composition, such as adverse pregnancy outcomes. Taken together, our findings demonstrate numerous biologically relevant pathways and phenotypes associated with vaginal microbiome traits. Limitations We found substantial functional overlap in several biologically relevant innate immunity pathways. This may in part be driven by the compositionality of individual taxa. To mitigate this, we limited examination to a few traits of known importance in conjunction with comprehensive community characterization. We also confirmed numerous SNPs in close proximity to genomic loci associated with innate immunity reported in previous studies of host genetic traits associated with BV and vaginal taxa. Although we identified novel candidate regions associated with vaginal microbiome traits, additional studies are needed to replicate our findings. Evaluation of functional impact with multi-omic studies (such as gene expression, epigenetics, and fine mapping) would allow mechanistic inference and aid in elucidating regulatory elements, which could lead to translational advances in optimizing the vaginal microbiome and preventing BV and associated consequences. Conclusions Given the multiple associations of important microbiome traits with various immune signaling pathways, the composition of the vaginal microbiome (and subsequently, BV risk) likely is influenced by host genetics through immune phenotypes. Replication studies and functional studies are needed to confirm and further elucidate understanding of how vaginal bacteria interact with the genetic make-up of the host to effect non-optimal vaginal microbiome and related outcomes. Given the co-occurrence of risk for BV, non-optimal vaginal microbiome, and HIV and STI among African and African American women, well-powered cross-national studies are needed to answer whether common variants are replicated across populations, and to identify important gene by environment interactions that inform how much risk for non-optimal vaginal microbiome may be modifiable, such as through behavioral modification or prevention or treatment of co-infections (e.g., HSV-2, HIV). Methods This study was approved by the Ethical Review Committee of Maseno University (Kisumu, Kenya; MSU/DRPC/MUERC/00054/13; January 13, 2014), and the Institutional Review Board of the University of Illinois at Chicago (USA; 2013-0511; February 12, 2014). Study Design and Participants Subjects in this analysis were enrolled in Afya Jozi, Afya Jamii (Kiswahili for “Healthy Pair, Healthy Community”), a prospective cohort study of heterosexual couples in Kisumu, Kenya. Recruitment and eligibility criteria have been previously published [48]. Briefly, we included men aged 18-35 years and their female partners aged 16 years and older, who independently confirmed a sexual relationship of at least 6 months duration. After the baseline visit, couples were scheduled for follow-up at 1 month, 6 months, and 12 months. Couples were enrolled from April 1, 2014, through June 22, 2016 and 12-month follow-up was completed June 21, 2017. Specimen Collection At each scheduled study visit, participants underwent a standardized medical history and physical examination, followed by a personal interview to obtain socio-demographic and behavioral information. At baseline and each follow-up visit, clinicians collected vaginal swabs for assessment of BV. Gram stained slides were evaluated according to Nugent’s criteria, and a score of 7-10 was defined as BV following clinical recommendations [49]. Vaginal swab collection was followed by collection of cervicovaginal lavage (CVL) in 10 ml sterile water. Aliquots of 2mL were stored at -80º until shipment to Chicago for processing. Vaginal Microbiome Characterization We used the vaginal microbiome as measured from the baseline visit for this analysis, because antimicrobial treatment was provided for BV and other cervicovaginal infections which may confound subsequent vaginal microbiome observations. DNA extraction, library preparation and sequencing were performed at the University of Illinois at Chicago Sequencing Core (UICSQC). DNA was extracted from CVL specimens using a PowerFecal DNA kit (Qiagen). A two-stage PCR protocol was used to amplify the V3-V4 variable region of bacterial 16S rRNA genes [50]. Illumina MiSeq was used to sequence the amplicons after pooling, implementing V3 chemistry (600 cycles). Quality control and taxonomic annotation were conducted by University of Maryland Institute for Genomic Science (UMD IGS) following previously published protocol [51]. Community state types (CSTs) were determined by hierarchical clustering of relative abundances of taxa, using VALENCIA algorithm implemented by UMD IGS, which uses a distance-based metric to classify each sample to a CST based on the similarity of that sample to the centroid of CSTs identified in a reference set [52]. Raw sequence data files are available in the Sequence Read Archive (National Center for Biotechnology Information; BioProject identifier PRJNA516684). Genotyping and Quality Control Genomic DNA was obtained from 200 Kenyan women using oral swabs and was extracted using QIAamp DNA blood mini kit (Qiagen). DNA extraction and isolation was performed at the Center for Population Epigenetics at Northwestern University. Study participants were genotyped using the Infinium Global Screening Array (~640,000 markers; Illumina, Inc., San Diego). The software Illumina GenomeStudio (v2.0.4, Illumina, Inc., San Diego) was used to call single nucleotide polymorphisms (SNPs) at the Genomic Facility, University of Chicago. Study participants with a genotyping call rate less than 95% were excluded from analysis as were study participants with missing vaginal microbiome traits. Due to cryptic relatedness identified during quality control, we restricted all analyses to the maximum number of unrelated individuals. Implementation of these exclusion criteria resulted in 171 study participants for analysis. SNPs with a call rate less than 95%, a minor allele frequency less than 1%, or a Hardy-Weinberg equilibrium P value less than 10 -6 were omitted. After these exclusion criteria, 336,151 remained for further analysis. Genotype Imputation We performed genotype imputation to identify additional SNPs associated with the vaginal microbiome traits that were not directly genotyped using the Luhya in Webuye, Kenya reference panel from the 1000 Genomes Project [53]. The program Shapeit2 [54] was used to phase genotypes and imputation was performed using Minimac3 [55]. Imputed genotypes were coded as allelic dosages (estimated counts ranging from 0 to 2). Low quality imputed SNPs, i.e. Rsq < 0.30 and MAF < 1%, were excluded from further analyses. Statistical Analysis We evaluated the association between single nucleotide polymorphisms (SNPs) with five vaginal microbiome traits: (1) presence of L. crispatus , relative abundances of (2) L. iners and (3) G. vaginalis , (4) Shannon diversity index, and (5) CST. We chose L. crispatus for its known importance in vaginal microbiome health, L. iners due to its predominance among Lactobacillus species in our sample and other African samples, and G. vaginalis due to its inclusion as a morphotype in Nugent scoring and determination of BV. For alpha diversity measures, we selected Shannon diversity index, as all alpha diversity measures were highly correlated (Spearman correlations, 0.77 – 0.98). Prior to analyses, the relative abundance of L. iners and Shannon diversity index were inverse log-transformed to approximate a more normal distribution ( Supplemental Figure 2 ). As transformation did not lead to normal approximation, the relative abundance of G. vaginalis was analyzed by quartile. Given the infrequency of L. crispatus (present in 24% of samples) we analyzed it as presence vs. absence. Of 171 subjects in the analysis, 168 (98%) baseline vaginal microbial communities were classified as CST-I (n=14; 0% with BV), CST-III (n=77; 5.2% with BV), or CST-IV (n=77; 43% with BV). There were three outliers (n=2 with CST-II, n=1 with CST-V), and these observations were excluded from CST analyses. BV was not analyzed as a separate outcome because it was collinear with CST. We analyzed CST as a linear outcome given the ordinal nature of BV risk, and to meet parameters for statistical software. Principal components of genetic ancestry were generated using the program EIGENSOFT [56] and the first three principal components were retained and included as covariates. Quantile-quantile (Q-Q) plots were generated for each trait to visualize test statistics and the genomic control inflation factors were calculated. We used PLINK (v1.90) [57] to test the associations between L. iners , G. vaginalis , Shannon diversity index, and CST with SNPs using linear regression, and association between L. crispatus and SNPs using logistic regression, adjusting for age and principal components. We assumed an additive genetic effects model for all analyses. To account for genotype uncertainty, the allelic dosages from imputed SNPs were analyzed using Mach2QTL for linear regression and Mach2DAT for logistic regression (see Web Resources). SNPs with a P value less than 1.49×10 -7 (0.05/336,151) were declared genome-wide significant. The software R (3.5.0) [58] and LocusZoom [59] (hg19/1000 Genomes AFR) were used for graphing. Pathway and Pleiotropy Analysis We performed pathway and pleiotropy analysis using SKAT-O [60] and WebGestalt [61] to examine the combined genetic effects on the underlying biological mechanisms influencing the vaginal microbiome traits. We mapped all directly genotyped SNPs to autosomal genes based on the genomic positions of the GRCh37/hg19 assembly and included ±20 kb gene boundary to capture proximal regulatory and functional elements that contribute to gene regulation. Gene-set associations were performed using SKAT-O, adjusting for age and the first three principal components. Over-representation analyses of pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome) and diseases / phenotypes (DisGeNET, GLAD4U, Online Mendelian Inheritance in Man (OMIM), and Human Phenotype Ontology) was analyzed using WebGestalt. Pathways, diseases, and phenotypes with a false discovery rate (FDR) P value < 0.05 after Benjamini-Hochberg multiple testing adjustment were declared significant. The top five pathways and diseases / phenotypes from WebGestalt are reported. Web Resources Mach2DAT, http://csg.sph.umich.edu/abecasis/MACH/download/ Mach2QTL, http://csg.sph.umich.edu/abecasis/MACH/download/ Supplemental Figure Information Supplemental Figure 1A-1E. Q-Q plots for five vaginal microbiome traits measured in 171 Kenyan women . Legend: Inspection of Q-Q plots for each microbiome trait evaluated indicate proper control of population stratification. Supplemental Figure 2A-E. Regional conditional association plots of the top genomic loci associated with vaginal microbiome traits. Legend: P values (−log10) of the GWAS (solid circle) on the y-axis are plotted against the genomic positions of each SNP on the x-axis for each microbiome trait. Genes in the region are shown below. The linkage disequilibrium (LD) values (r 2 ) between the lead SNP and the other SNPs are indicated in different colors. Declarations Ethics approval and consent to participate : This study was approved by the Ethical Review Committee of Maseno University (Kisumu, Kenya; MSU/DRPC/MUERC/00054/13; January 13, 2014), and the Institutional Review Board of the University of Illinois at Chicago (USA; 2013-0511; February 12, 2014). Written informed consent was obtained from all participants in their language of choice (English, DhoLuo, or Kiswahili). Consent for publication : Not applicable. Availability of data and material : The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests : The authors declare that they have no competing interests Funding : This study was supported by grant number R01-AI110369 (PI: Mehta) from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of Microbiology, and by the National Cancer Institute of the National Institutes of Health under award number U54CA221205 (MPI: Hou, Murphy). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Authors' contributions : SDM : Obtained funding; study conceptualization and design; drafted manuscript. DN : Design and implementation of statistical analysis approach; visualization; critical review and revision of manuscript FO : Study oversight and management to ensure integrity to protocols; critical review and revision of manuscript SJG : Development and oversight of protocols for amplicon sequencing; microbiologic analyses and interpretation; critical review and revision of manuscript WA : Development, implementation, and oversight of laboratory protocols in Kenya; acquisition of data; microbiologic analyses and interpretation; critical review and revision of manuscript. AL : Critical review and revision of manuscript. YZ : Design and interpretation of statistical analysis approach; critical review and revision of manuscript LH : Selection of GWAS methods; design of analysis; interpretation of results; critical review and revision of manuscript. Acknowledgements: Not applicable Authors' information (optional) : Not applicable References Torrone EA, Morrison CS, Chen PL, Kwok C, Francis SC, Hayes RJ, Looker KJ, McCormack S, McGrath N, van de Wijgert J, et al: Prevalence of sexually transmitted infections and bacterial vaginosis among women in sub-Saharan Africa: An individual participant data meta-analysis of 18 HIV prevention studies. PLoS Med 2018, 15: e1002511. Atashili J, Poole C, Ndumbe PM, Adimora AA, Smith JS: Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies. AIDS 2008, 22: 1493-1501. Lewis FM, Bernstein KT, Aral SO: Vaginal Microbiome and Its Relationship to Behavior, Sexual Health, and Sexually Transmitted Diseases. Obstet Gynecol 2017, 129: 643-654. van de Wijgert J, Jespers V: The global health impact of vaginal dysbiosis. Res Microbiol 2017, 168: 859-864. Fredricks DN: Molecular methods to describe the spectrum and dynamics of the vaginal microbiota. 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Baseline participant characteristics and vaginal microbiome composition overall and stratified by community state type*. Total, N=171 n (%) CST I, N=14 n (%) CST-III, N=77 n (%) CST-IV, N=77 n (%) Median age in years (IQR) 22 (20-25) 24.5 (19-28) 23 (20-25) 22 (20-25) HIV status Negative Positive Missing 152 (89.9) 17 (10.1) 2 14 (100) 70 (92.1) 6 (7.9) 1 65 (85.5) 11 (14.5) 1 HSV-2 status Negative Positive 81 (47.4) 90 (52.6) 12 (85.7) 2 (14.3) 39 (50.6) 38 (49.4) 28 (36.4) 49 (63.6) Circumcised male sex partner 91 (53.2) 6 (42.9) 43 (55.8) 40 (52.0) BV (Nugent score 7-10) at baseline 37 (21.6) 0 (0) 4 (5.2) 33 (42.9) Proportion of visits with BV over follow-up 0% 25% >25%-50% >50%-75% 100% 89 (52.1) 22 (12.9) 33 (20.2) 19 (11.1) 8 (4.7) 14 (100) 49 (63.6) 10 (13.0) 11 (14.3) 7 (9.1) 25 (32.5) 11 (14.3) 21 (27.3) 12 (15.5) 8 (10.4) Presence of L. crispatus at baseline 42 (24.6) 14 (100) 22 (28.6) 6 (7.8) Mean RA L. crispatus if present (SD) 28.2 (35.3) 72.5 (21.6) 7.71 (13.0) 0.21 (0.34) Presence of L. iners at baseline 142 (83.0) 5 (35.7) 77 (100) 58 (75.3) Mean RA L. iners if present (SD) 44.8 (42.4) 1.84 (3.24) 80.3 (23.2) 2.99 (5.11) Presence of G. vaginalis at baseline 129 (75.4) 7 (50.0) 46 (59.7) 73 (94.8) Mean RA G. vaginalis if present (SD) 23.1 (24.8) 20.9 (15.0) 6.81 (10.8) 33.7 (26.7) Median Shannon diversity index (IQR) 0.94 (0.30 – 1.82) 0.80 (0.33 – 0.98) 0.34 (0.16 – 0.83) 1.84 (1.20 – 2.17) IQR = Interquartile range; BV = Bacterial vaginosis; RA = Relative abundance; SD = Standard Deviation * CST-IV combined sub-types A (n=9), B (n=62), and C (n=6). Three observations (n=2 with CST-II, n=1 with CST-V) are not included in this table. Table 2. Top single nucleotide polymorphisms associated with five vaginal microbiome traits. SNP Chr Position Gene A1/A2 MAF b P L. crispatus rs73330467 5 125694420 LOC101927488 -GRAMD2B G/T 0.07 11.58 * 4.79E-06 L. iners rs527430 1 47918821 FOXD2- TRABD2B A/G 0.06 1.05 6.98E-07 rs77007265 2 31384829 GALNT14-CAPN14 C/A 0.08 -0.93 2.07E-06 rs17010778 2 31384974 GALNT14-CAPN14 C/T 0.06 -1.00 3.60E-06 rs12221275 10 122972398 WDR11-FGFR2 A/C 0.01 2.22 6.95E-06 G. vaginalis rs1229660 7 26437429 SNX10- LOC441204 C/T 0.10 -0.99 4.65E-06 rs10414170 19 57246309 ZNF835-ZIM2-AS1 C/A 0.30 -0.62 6.56E-06 Shannon Diversity Index rs7632135 3 154455745 GPR149-MME G/A 0.24 -0.59 4.37E-06 rs3097137 5 73330562 ARHGEF28 - LINC01335 A/G 0.20 0.56 4.25E-06 rs112627544 7 1929410 MAD1L1 T/G 0.42 -0.47 9.04E-06 rs6970796 7 1947895 MAD1L1 T/C 0.36 -0.50 2.25E-06 rs56952063 14 95107145 SERPINA13P C/T 0.08 -0.90 9.65E-06 rs972741 16 25468083 ZKSCAN2-HS3ST4 A/G 0.19 0.66 8.52E-07 Community State Type rs419816 5 52571758 LOC257396-FST C/T 0.13 0.45 9.99E-06 rs1929353 9 3759975 RFX3-AS1-GLIS3 G/A 0.24 0.35 9.51E-06 rs2302902 12 96617304 ELK3 T/C 0.20 0.41 3.09E-06 SNP, Single nucleotide polymorphism; Chr, Chromosome; A1/A2, allele 1 / allele 2; MAF, Minor allele frequency. SNPs with a P <1 ´ 10 -5 for each trait are included in the table. Gene name is in boldface if the SNP is located within the gene. * Reported as odds ratio Table 3. Results of pathway analysis: Top KEGG and Reactome pathways associated with vaginal microbiome traits. Trait Pathway Observed/Total Genes P Adjusted P * L. crispatus Metabolism of amino acids and derivatives 29/370 7.27E-06 1.10E-02 GPCR ligand binding 32/457 2.46E-05 1.37E-02 PCP/CE pathway 11/92 1.50E-04 3.97E-02 Beta-catenin independent WNT signaling 14/145 2.04E-04 4.72E-02 Neutrophil degranulation 30/479 3.12E-04 5.31E-02 L. iners Toll-like receptor cascades 17/155 8.41E-06 9.76E-03 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 13/95 8.82E-06 9.76E-03 Toll like receptor TLR6:TLR2 cascade 13/95 8.82E-06 9.76E-03 Toll like receptor TLR1:TLR2 cascade 13/98 1.25E-05 9.76E-03 Toll like receptor 2 (TLR2) cascade 13/98 1.25E-05 9.76E-03 G. vaginalis Signaling by GPCR 66/1162 5.35E-07 1.46E-03 GPCR downstream signaling 63/1100 7.45E-07 1.46E-03 Neutrophil degranulation 29/479 3.11E-04 2.44E-01 G alpha (s) signaling events 31/536 4.29E-04 2.80E-01 Formation of the cornified envelope 12/129 5.23E-04 2.93E-01 Shannon Diversity Index Class B/2 (secretin family receptors) 12/95 1.89E-05 3.71E-02 RNA polymerase II transcription 62/1292 6.53E-05 5.12E-02 Gene expression (transcription) 66/1430 1.19E-04 6.52E-02 Neuronal system 24/368 1.99E-04 6.52E-02 Cleavage of growing transcript in the termination region 8/67 6.80E-04 9.52E-02 Community State Type Human T-cell leukemia virus 1 infection 20/255 8.77E-05 9.30E-03 Class B/2 (secretin family receptors) 11/95 1.23E-04 1.06E-02 GPCR ligand binding 29/457 1.25E-04 1.06E-02 Post-translational modification: synthesis of GPI-anchored proteins 10/92 4.17E-04 1.89E-02 Transmission across chemical synapses 17/227 4.95E-04 2.12E-02 * P -values are Benjamini-Hochberg adjusted Table 4. Results of pleiotropy analysis: Top phenotypes associated with vaginal microbiome traits. Trait Phenotype Observed/Total Genes P Adjusted P * L. crispatus Bacterial infections 23/260 9.25E-06 1.10E-02 Meckel syndrome (MKS) 17/164 1.78E-05 1.37E-02 Hypertension, pulmonary 15/137 2.88E-05 1.37E-02 Varicose veins 11/79 3.64E-05 1.45E-02 Gram-positive bacterial infections 17/181 6.29E-05 2.15E-02 L. iners Autosomal dominant inheritance 72/1403 3.17E-05 1.78E-02 Growth abnormality 88/1822 3.89E-05 1.91E-02 Abnormality of the cardiovascular system 86/1796 6.49E-05 2.83E-02 Aplasia/hypoplasia involving the vertebral column 8/55 3.08E-04 8.05E-02 Abnormality of hair density 20/267 3.35E-04 8.05E-02 G. vaginalis Pancreatic neoplasm 11/88 6.51E-05 8.52E-02 Carcinoma, pancreatic ductal 13/139 2.95E-04 2.44E-01 Pancreatic neoplasms 19/281 9.08E-04 3.56E-01 Neoplasm of the endocrine system 9/89 1.42E-03 4.11E-01 Thyroid neoplasms 13/165 1.48E-03 4.11E-01 Shannon Diversity Index Abnormality of the female genitalia 33/505 1.31E-05 3.71E-02 Abnormality of female internal genitalia 29/444 4.38E-05 5.12E-02 Abnormal internal genitalia 30/473 5.57E-05 5.12E-02 Abnormality of the uterus 15/176 1.92E-04 6.52E-02 Abnormality of the ovary 16/196 1.96E-04 6.52E-02 Community State Type Serotonin syndrome 23/134 1.18E-11 4.39E-08 Abnormality of the integument 99/1920 5.16E-08 1.01E-04 Autosomal dominant inheritance 74/1403 1.33E-06 1.50E-03 Prader-Willi syndrome 20/195 1.70E-06 1.50E-03 Abnormality of the skin 80/1572 1.92E-06 1.50E-03 * P -values are Benjamini-Hochberg adjusted Supplemental Table 1. Excel File. Details of Candidate Gene Analysis Findings Supplementary Files SupplementalFigure2BLinerscondzoom.png SupplementalFigure2ECSTcondzoom.png SupplementalFigure2DShannoncondzoom.png SupplementalFigure2CGvagcondzoom.png SupplementalFigure2ALcrispcondzoom.png SupplementalFigure1ECSTqq.png SupplementalFigure1BLinersqq.png SupplementalFigure1DShannonqq.png SupplementalFigure1CGvagqq.png GWASN171finalanalyticdataset.csv SupplTableCandidateDetailsFinalComplete.xlsx SupplementalFigure1ALcrispqq.png Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-17153","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":405377,"identity":"f2a21fbf-5d0d-440e-a421-5b18a2b2f9cf","order_by":1,"name":"Supriya D Mehta","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYBAC+QYgkcDAwNjPwAhiMhPWYnAAqmVmA9FaoDTjhgNgmhgtErnHPjxss5PdfCO58QNDhXViAyEt8jPykmcktiUbb7uR2CzBcCadsBaGGznGDIltzIlALW0MjG2HidZSn7h5BkjLP+K1HE7cIAHS0kCEFoMz75IZEs4dN55x5mGzRMKxdGOCWuTbcw8z/iirlu1vT3/44UONtSxhhzHwACOFDcpOIKwcqoXhD3FKR8EoGAWjYIQCAGtAQ0sdwMgeAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-7926-2489","institution":"University of Illinois at Chicago","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Supriya","middleName":"D","lastName":"Mehta","suffix":""},{"id":405378,"identity":"73ebab1e-abf3-4f63-9ba2-04f5961a6988","order_by":2,"name":"Drew R Nannini","email":"","orcid":"","institution":"Northwestern University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Drew","middleName":"R","lastName":"Nannini","suffix":""},{"id":405379,"identity":"f6e2f12f-97c2-4359-9b4c-b702b7524b2c","order_by":3,"name":"Fredrick Otieno","email":"","orcid":"","institution":"Nyanza Reproductive Health Society","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fredrick","middleName":"","lastName":"Otieno","suffix":""},{"id":405380,"identity":"cdf5eacb-6928-4a17-9ef6-57aad46ee983","order_by":4,"name":"Stefan J. Green","email":"","orcid":"","institution":"University of Illinois at Chicago","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Stefan","middleName":"J.","lastName":"Green","suffix":""},{"id":405381,"identity":"c7a349e6-cf3f-45b3-812a-7f9391aef009","order_by":5,"name":"Walter Agingu","email":"","orcid":"","institution":"Nyanza Reproductive Health Society","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Walter","middleName":"","lastName":"Agingu","suffix":""},{"id":405382,"identity":"de9bafa8-e863-4bc4-8758-ab028925ec84","order_by":6,"name":"Alan Landay","email":"","orcid":"","institution":"Rush University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alan","middleName":"","lastName":"Landay","suffix":""},{"id":405383,"identity":"1183d8e5-6f9a-49f0-97ea-7b584c1f89c6","order_by":7,"name":"Yinan Zheng","email":"","orcid":"","institution":"Northwestern University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yinan","middleName":"","lastName":"Zheng","suffix":""},{"id":405384,"identity":"e1b2d2b8-4003-41bc-8dee-fb56c36c29d1","order_by":8,"name":"Lifang Hou","email":"","orcid":"","institution":"Northwestern University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lifang","middleName":"","lastName":"Hou","suffix":""}],"badges":[],"createdAt":"2020-03-11 12:46:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-17153/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-17153/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":643518,"identity":"9e0c3452-6c14-4b4a-bdbf-e2368f68bc06","added_by":"auto","created_at":"2020-03-13 15:03:05","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":624125,"visible":true,"origin":"","legend":"Manhattan plots for single nucleotide polymorphisms associated with vaginal microbiome traits.\nLegend: The x-axis corresponds to the genomic position, and the y-axis shows the −log10 of the P-value. The horizontal dashed line corresponds to the genome-wide significance threshold.","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/1.png"},{"id":643522,"identity":"44f35878-9d82-49c2-bd97-f6989826deaf","added_by":"auto","created_at":"2020-03-13 15:03:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":756388,"visible":true,"origin":"","legend":"Regional association plots of the top genomic loci associated with vaginal microbiome traits.\nLegend: P values (−log10) of the GWAS (solid circle) on the y-axis are plotted against the genomic positions of each SNP on the x-axis for each microbiome trait. Genes in the region are shown below. The linkage disequilibrium (LD) values (r2) between the lead SNP and the other SNPs are indicated in different colors.","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/2.png"},{"id":643523,"identity":"a04b6001-642f-4bc1-bc90-39a1f7d700cd","added_by":"auto","created_at":"2020-03-13 15:03:06","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":72739,"visible":true,"origin":"","legend":"Heatmap summarizing beta coefficients for the most significant SNPs within 100kbp of previoulsy reported SNPs.\nLegend: The heatmap on the left represents the direction and magnitude of the coefficients (beta) for the SNPs within 100kb associated with five vaginal microbiome traits: (A) relative abundance L. iners, (B) presence of L. crispatus, (C) relative abundance G. vaginalis, (D) Shannon diversity index, (E) Community State Type (CST), with CST-IV as the reference. Negative coefficients are shaded in blue and positive coefficients are shaded in red, with deeper intensity representing the magnitude of the coefficient. The heatmap on the right represents the P-value of the corresponding coefficients for SNPs and vaginal microbiome traits (A-E). All associations shown have p-value\u003c0.05. The Bonferroni cutoff for significance is \u003c0.00102, and these p-values are shaded yellow to purple. P-values \u003e0.00102-0.05 are shaded grey.","description":"","filename":"Figure3heatmapbetasandSNPs20FEB20.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/Figure 3 heatmap betas and SNPs 20-FEB-20.png"},{"id":13493572,"identity":"4f1a0df0-b8dc-4fe9-a863-7f074412334b","added_by":"auto","created_at":"2021-09-16 22:36:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2372208,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/141cea39-0574-401e-9d2c-f90e1b988ace.pdf"},{"id":643531,"identity":"233fb2fa-847e-47bd-b71d-99f91bd4bd50","added_by":"auto","created_at":"2020-03-13 15:03:07","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":108265,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalFigure2BLinerscondzoom.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/Supplemental_Figure_2B_Liners_condzoom.png"},{"id":643530,"identity":"d15e8d0c-a02d-423a-b39d-ccc937cce10b","added_by":"auto","created_at":"2020-03-13 15:03:07","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":106212,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalFigure2ECSTcondzoom.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/Supplemental_Figure_2E_CST_condzoom.png"},{"id":643529,"identity":"ce1022e9-80ff-44ff-a26d-9e1bb8774472","added_by":"auto","created_at":"2020-03-13 15:03:07","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":114835,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalFigure2DShannoncondzoom.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/Supplemental_Figure_2D_Shannon_condzoom.png"},{"id":643528,"identity":"2ff63f18-fc7e-467a-ae32-c218c1bc41e4","added_by":"auto","created_at":"2020-03-13 15:03:07","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":104141,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalFigure2CGvagcondzoom.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/Supplemental_Figure_2C_Gvag_condzoom.png"},{"id":643527,"identity":"4bc76474-7e10-485c-a90d-40af5c118284","added_by":"auto","created_at":"2020-03-13 15:03:07","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":103135,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalFigure2ALcrispcondzoom.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/Supplemental_Figure_2A_Lcrisp_condzoom.png"},{"id":643526,"identity":"0d0970a2-9425-4f5c-85e5-a55d6879c281","added_by":"auto","created_at":"2020-03-13 15:03:07","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":27270,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalFigure1ECSTqq.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/Supplemental_Figure_1E_CST_qq.png"},{"id":643525,"identity":"8e611613-018c-4610-96a1-9d760b7ff86d","added_by":"auto","created_at":"2020-03-13 15:03:06","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":25647,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalFigure1BLinersqq.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/Supplemental_Figure_1B_Liners_qq.png"},{"id":643524,"identity":"c078e00b-0088-4204-b19c-e2163118215f","added_by":"auto","created_at":"2020-03-13 15:03:06","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":28505,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalFigure1DShannonqq.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/Supplemental_Figure_1D_Shannon_qq.png"},{"id":643521,"identity":"f6c8170c-9b22-45f5-9a45-7c6b76327188","added_by":"auto","created_at":"2020-03-13 15:03:06","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":25512,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalFigure1CGvagqq.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/Supplemental_Figure_1C_Gvag_qq.png"},{"id":643520,"identity":"504bd90d-20ec-48a8-a2f5-2819e12fb68f","added_by":"auto","created_at":"2020-03-13 15:03:06","extension":"csv","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":18596,"visible":true,"origin":"","legend":"","description":"","filename":"GWASN171finalanalyticdataset.csv","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/GWAS N=171 final analytic dataset.csv"},{"id":643519,"identity":"56f81aea-09dd-4f2a-8fa8-bf838aa3291c","added_by":"auto","created_at":"2020-03-13 15:03:06","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":30030,"visible":true,"origin":"","legend":"","description":"","filename":"SupplTableCandidateDetailsFinalComplete.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/Suppl_Table_Candidate_Details_Final_Complete.xlsx"},{"id":643517,"identity":"48bad2f9-199e-479c-a666-a6cd43460424","added_by":"auto","created_at":"2020-03-13 15:03:05","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":25983,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalFigure1ALcrispqq.png","url":"https://assets-eu.researchsquare.com/files/rs-17153/v1/Supplemental_Figure_1A_Lcrisp_qq.png"}],"financialInterests":"","formattedTitle":"Host Genetic Determinants of the Vaginal Microbiome in Kenyan Women","fulltext":[{"header":"Introduction","content":" \u003cp\u003eBacterial vaginosis (BV) is a condition of clinical and public health significance. BV is prevalent in 20\u0026ndash;50% of women in sub-Saharan Africa [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In a meta-analysis, Atashili et al. estimated the relative risk of HIV acquisition to be 1.6 times higher for women with BV, equating to a population attributable fraction of 15% due to the high population prevalence [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. BV is also associated with an increased likelihood of sexually transmitted infections (STI) and adverse pregnancy outcomes [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. BV represents a polymicrobial shift in the vaginal microbiome, often from a \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eLactobacillus\u003c/span\u003e dominant community to one that is diverse, with multiple species of anaerobic bacteria [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In particular, \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eL. crispatus\u003c/span\u003e enrichment has been shown to be protective against BV, HIV, and STIs [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBV is considered a sexually enhanced infection, and individuals with new or multiple sex partners, those who engage in unprotected vaginal sex, or those whose sex partner is uncircumcised are at an increased risk of BV [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In addition to sexual risk factors, non-sexual risk factors that are associated with BV include intravaginal and vaginal hygiene practices [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], cigarette smoking [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and race/ethnicity [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In numerous studies, women of African descent have increased risk of BV and non-optimal vaginal microbiome composition [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These associations with race persist even when controlling for socio-demographics and sexual practices [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], leading to the hypothesis that genetic factors may influence the vaginal microbiome composition and subsequently BV [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo date, a limited number of studies have examined the host genetic contribution to the vaginal flora and BV. Primarily these studies have focused on host differences in candidate genes responsible for inflammatory mucosal immune response in other infectious conditions [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. As reviewed by Turovskiy et al., studies have targeted single nucleotide polymorphisms (SNPs) in: (1) Toll-like receptor (TLR) genes because of their role in recognizing potential threats and initiating inflammatory responses and activating other immune cells, and (2) pro-inflammatory and inflammatory cytokines (e.g., IL-1β, TNF-α) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Most of these studies, however, evaluated SNPs in relation to BV or to specific taxa associated with BV (e.g., \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eG. vaginalis\u003c/span\u003e, \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eA. vaginae\u003c/span\u003e spp.) and none of the studies measured the vaginal microflora or host genetic contribution comprehensively, such as with cultivation-independent molecular microbial characterization or a genome wide association study (GWAS), respectively.\u003c/p\u003e \u003cp\u003eTo address this gap, we conducted GWAS on vaginal microbiome traits among native Kenyan women. We hypothesized that by conducting GWAS, we would identify novel genomic loci associated with vaginal microbiome traits, furthering our understanding of the underlying genetic factors. Identifying genetic variants may aid in elucidating the biological mechanisms associated with these complex vaginal microbiome traits and associated diseases. Complementary to GWAS, we conducted replication analyses of SNPs previously reported to be associated with vaginal microflora or BV.\u003c/p\u003e "},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eStudy Sample\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAmong 171 women included in this analysis, the prevalence of BV at baseline was 22% (\u003cstrong\u003eTable 1\u003c/strong\u003e). Over half (53%) of women were HSV-2 seropositive and 10% were HIV positive, which is in keeping with the prevalence of HIV among women in this age range in the general population in this region of western Kenya [18]. \u003cem\u003eL. crispatus \u003c/em\u003ewas present in 25% of samples (28% mean relative abundance), \u003cem\u003eL. iners \u003c/em\u003ewas present in 83% of samples (mean relative abundance 45%), and \u003cem\u003eG. vaginalis \u003c/em\u003ewas present in 75% of samples (25% mean relative abundance).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eGenome-wide association results\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe genomic control (GC) inflation factor, l, was 1.01, 1.00, 1.00, 1.00, and 1.00 for \u003cem\u003eL. crispatus\u003c/em\u003e, \u003cem\u003eL. iners\u003c/em\u003e, \u003cem\u003eG. vaginalis\u003c/em\u003e, the Shannon diversity index, and CST, respectively, after adjusting for age and the first three principal components. Upon visual inspection of the Q-Q plots (\u003cstrong\u003eSupplementary Figure 1\u003c/strong\u003e), the observed \u003cem\u003eP\u003c/em\u003e values do not deviate from the null, except at the extreme tail. Together with the genomic inflation factors, the Q-Q plots indicate proper control of population stratification.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1A-E\u003c/strong\u003e displays the Manhattan plots of the genome-wide \u003cem\u003eP\u003c/em\u003e values for each vaginal microbiome trait. \u003cstrong\u003eTable 2\u003c/strong\u003e summarizes the top SNPs (\u003cem\u003eP\u003c/em\u003e \u0026lt; 1 x 10\u003csup\u003e-5\u003c/sup\u003e) for each vaginal microbiome trait and minor allele frequencies (MAF) derived from our data. Overall, no SNP reached genome-wide significance (0.05/336,151 = 1.49E-07). The SNP with the lowest adjusted p-value associated with presence of \u003cem\u003eL. crispatus \u003c/em\u003ewas rs73330467 (\u003cem\u003eP\u003c/em\u003e = 4.79 x 10\u003csup\u003e-6\u003c/sup\u003e, \u003cstrong\u003eFigure 1A\u003c/strong\u003e), located in an intergenic region between \u003cem\u003eLOC101927488\u003c/em\u003e and \u003cem\u003eGRAMD2B\u003c/em\u003e on chromosome 5. The minor allele G (MAF = 0.07) was associated with an 11.6-fold increased odds of detecting \u003cem\u003eL. crispatus\u003c/em\u003e. The most significant SNP associated with relative abundance of \u003cem\u003eL. iners \u003c/em\u003ewas rs527430 (\u003cem\u003eP\u003c/em\u003e = 6.98 x 10\u003csup\u003e-7\u003c/sup\u003e, \u003cstrong\u003eFigure 1B\u003c/strong\u003e) on chromosome 1, located in an intergenic region between \u003cem\u003eFOXD2\u003c/em\u003e and \u003cem\u003eTRABD2B\u003c/em\u003e. The minor allele A (MAF = 0.06) was associated with an increase in relative abundance of \u003cem\u003eL. iners\u003c/em\u003e (\u0026beta; = 1.05). The most significant SNP associated with \u003cem\u003eG. vaginalis\u003c/em\u003e was rs1229660 (\u003cem\u003eP \u003c/em\u003e= 4.65 x 10\u003csup\u003e-6\u003c/sup\u003e, \u003cstrong\u003eFigure 1C\u003c/strong\u003e) located between \u003cem\u003eSNX10-LOC441204 \u003c/em\u003eon chromosome 7. The minor allele C (MAF = 0.10) was associated with a decrease in \u003cem\u003eG. vaginalis\u003c/em\u003e relative abundance (\u0026beta; = -0.99). The most significant SNP associated with Shannon diversity index was rs972741 (\u003cem\u003eP \u003c/em\u003e= 8.52 x 10\u003csup\u003e-7\u003c/sup\u003e, \u003cstrong\u003eFigures 1D\u003c/strong\u003e) located between \u003cem\u003eZKSCAN2\u003c/em\u003e and \u003cem\u003eHS3ST4 \u003c/em\u003eon chromosome 16. The minor allele A (MAF = 0.19) was associated with an increase in the Shannon diversity index (\u0026beta;= 0.66). The most significant SNP associated with CST was rs2302902 (\u003cem\u003eP \u003c/em\u003e= 3.09 x 10\u003csup\u003e-6\u003c/sup\u003e, \u003cstrong\u003eFigure 1E\u003c/strong\u003e) located in \u003cem\u003eELK3\u003c/em\u003e on chromosome 12. The minor allele T (MAF = 0.20) was associated with an increased likelihood of membership in lower diversity CST-I and CST-II as compared to CST-IV (\u0026beta;= 0.41).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eResults from Imputed SNPs\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe performed genotype imputation in order to expand genomic coverage and interrogate additional SNPs not directly genotyped. After removing SNPs with low imputation quality and low frequency (Rsq \u0026lt; 0.30 and MAF \u0026lt; 1%), several imputed SNPs (but no additional genomic regions) were identified. \u003cstrong\u003eFigure 2\u003c/strong\u003e presents the regional SNP association plots for each of the vaginal microbiome traits. Within the \u003cem\u003eZKSCAN2-HS3ST4 \u003c/em\u003eintergenic region on chromosome 16, several imputed SNPs were more significantly associated with the Shannon diversity index than those directly genotyped (\u003cstrong\u003eFigure 2E\u003c/strong\u003e). The most significant SNP in this region was rs115869045 (\u003cem\u003eP \u003c/em\u003e= 4.77 x 10\u003csup\u003e-7\u003c/sup\u003e, Rsq = 0.70).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConditional Analyses\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted conditional analyses for the genomic loci in which the most significant SNP was identified for each vaginal microbiome trait to determine whether additional SNPs contribute to the observed associations. \u003cstrong\u003eSupplementary Figure 2\u003c/strong\u003e displays the regional SNP associations conditioning on the most significant directly genotyped SNP by including the SNP as a covariate in the regression model. As shown in each plot, all of the immediate SNP associations reduced towards the null, suggesting the SNPs identified are the leading SNPs for the observed associations.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAnalysis of Previously Reported Loci\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe investigated the associations of previously reported SNPs in relation to BV or vaginal microflora to determine whether these associations are relevant in a Kenyan population. \u003cstrong\u003eFigure 3\u003c/strong\u003e and \u003cstrong\u003eSupplemental Table 1\u003c/strong\u003e summarize these findings. Overall, 49 autosomal SNPs were identified from previous studies, of which 45 SNPs exhibited high imputation quality (Rsq \u0026sup3; 0.30). When analyzed, 7 SNPs for \u003cem\u003eL. iners\u003c/em\u003e, 8 SNPs for \u003cem\u003eL. crispatus\u003c/em\u003e, 6 SNPs for \u003cem\u003eG. vaginalis\u003c/em\u003e, 10 SNPs for the Shannon Diversity Index, and 8 SNPs for CST had a \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 in our sample. These findings, however, were not significant after applying a Bonferroni correction (0.05 / 49 = 0.00102).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo replicate genomic loci associated with the microbiome traits, we extracted the most significant imputed SNP within \u0026plusmn; 100 kb of the previously reported SNPs for each microbiome trait in our study. This approach resulted in 6 genomic regions for \u003cem\u003eL. iners\u003c/em\u003e, 1 genomic region for \u003cem\u003eG. vaginalis\u003c/em\u003e, 7 genomic regions for Shannon Diversity Index, and 4 genomic regions for CST that were significant after Bonferroni correction (\u003cstrong\u003eFigure 3, Supplemental Table 1\u003c/strong\u003e). No regions were significant after multiple testing correction for \u003cem\u003eL. crispatus\u003c/em\u003e. The replicated genomic regions include \u003cem\u003eIL1RN\u003c/em\u003e (CST), \u003cem\u003eIL5\u003c/em\u003e (Shannon), \u003cem\u003eIL5RA \u003c/em\u003e(\u003cem\u003eL. iners, \u003c/em\u003eShannon), \u003cem\u003eIL-8\u003c/em\u003e (Shannon, CST), \u003cem\u003eTIRAP \u003c/em\u003e(\u003cem\u003eL. iners\u003c/em\u003e, Shannon), \u003cem\u003eTLR2 \u003c/em\u003e(Shannon, CST), \u003cem\u003eTLR3 \u003c/em\u003e(\u003cem\u003eL. iners, Shannon)\u003c/em\u003e, \u003cem\u003eTLR4 \u003c/em\u003e(\u003cem\u003eL. iners\u003c/em\u003e), \u003cem\u003eMBL2\u003c/em\u003e (\u003cem\u003eL. iners\u003c/em\u003e, \u003cem\u003eG. vaginalis\u003c/em\u003e, CST), and \u003cem\u003eMYD88 \u003c/em\u003e(\u003cem\u003eL. iners, \u003c/em\u003eShannon).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePathway and Pleiotropy Analyses \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e presents the top five KEGG and Reactome pathways from WebGestalt for each vaginal microbiome trait. Four pathways were significantly associated with \u003cem\u003eL. crispatus\u003c/em\u003e after Benjamini-Hochberg multiple testing adjustment, including G-protein-coupled receptor (GPCR) ligand binding and neutrophil degranulation. Five pathways were associated with \u003cem\u003eL. iners\u003c/em\u003e: 4 related to TLR cascades, and one to the TLR upstream component (MyD88:Mal TIRAP; MyD88-adaptor-like TIR-domain containing adaptor protein). Two biological pathways related to GPCR signaling were associated with \u003cem\u003eG. vaginalis\u003c/em\u003e, as well as \u0026lsquo;neutrophil degranulation\u0026rsquo;, though it did not meet Bonferroni significance. Similarly, two pathways were associated with CST, including the most significant pathway \u0026lsquo;Class B/2 (secretin family receptors)\u0026rsquo;, and one pathway was associated with the Shannon diversity index, \u0026lsquo;Class B/2 (secretin family receptors)\u0026rsquo;.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e summarizes the top five DisGeNET, GLAD4U, OMIM, and Human Phenotype Ontology terms from WebGestalt for each vaginal microbiome trait. Five phenotypes were significantly associated with \u003cem\u003eL. crispatus\u003c/em\u003e after Benjamini-Hochberg multiple testing adjustment, including \u0026lsquo;Bacterial infections\u0026rsquo; (\u003cem\u003eP\u003c/em\u003e = 0.011) as the most significant phenotype. Three phenotypes were associated with \u003cem\u003eL. iners\u003c/em\u003e, with \u0026lsquo;Autosomal dominant inheritance\u0026rsquo; the most significant (\u003cem\u003eP\u003c/em\u003e = 0.018). No phenotypes were significantly associated with \u003cem\u003eG. vaginalis\u003c/em\u003e. One phenotype was associated with the Shannon diversity index, \u0026lsquo;Abnormality of the female genitalia\u0026rsquo; (\u003cem\u003eP\u003c/em\u003e = 0.037). Five phenotypes were associated with CST, including \u0026lsquo;Abnormality of the integument\u0026rsquo; (\u003cem\u003eP\u003c/em\u003e = 0.00023).\u003c/p\u003e"},{"header":"Discussion","content":" \u003cp\u003eTo our knowledge, this is the first GWAS of vaginal microbiome traits. In native Kenyan women, we identified novel genomic loci and biological pathways with biological relevance to host immunity, cell signaling, and infection, supporting the role of host genetics in inter-individual variability in vaginal microbiome traits.\u003c/p\u003e \u003cp\u003eIn GWAS, the most significant SNP associated with CST (rs2302902) is located in an intron of \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eELK3\u003c/span\u003e, a member of the ETS transcription factor family, which has not been previously associated with any vaginal microbiome traits or BV. Proteins in the \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eELK3\u003c/span\u003e subfamily are recruited by serum response factor and participate in transcription regulation, and has been associated in various cancers [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], including HPV-positive tumors of oropharyngeal cancer [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]and HPV16 in cervical tumors [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In meta-analysis, molecular and clinical measure of BV is associated with two-fold increase in risk of high-grade cervical epithelial neoplasia (CIN) or cancer [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Non-optimal vaginal microbiome leads to mucosal disruption and a pro-inflammatory environment that can facilitate HPV acquisition [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], but there may also be underlying shared or synergistic mechanism with ELK3. Other SNPs identified in GWAS occurred primarily in intergenic regions that haven\u0026rsquo;t previously been associated with BV or vaginal microbiome traits, and should be assessed for replication in future studies.\u003c/p\u003e \u003cp\u003eBV was absent from CST-I (\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eL. crispatus\u003c/span\u003e dominant) and infrequent (5.1%) in CST-III. Although CST-IV accounted for 89% of BV cases in this sample, 57% of women in CST-IV did \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003enot\u003c/span\u003e have BV. This is in keeping with many other studies: women with diverse CSTs are much more likely to have BV, but as many as 50% of women with these CSTs do not have BV [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Host genetics may partially explain this variability. For example, women with similar vaginal bacterial colonization (such as those within CST-IV) may have different \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eresponse\u003c/span\u003e to bacterial colonization depending on genetic traits. For women who mount an inflammatory response, this immune response may potentiate BV rather being solely a response to BV. In our study, restricting analyses to HIV uninfected women did not change our findings. This is not entirely unexpected, as associations between HIV and subsequent impact on the vaginal microbiome are variable, with some finding no effect [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Conversely, there is substantial data that demonstrate the temporal association between non-optimal vaginal microbiome composition, mucosal inflammation, and subsequent HIV risk [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], and our results suggest that host genetic differences may underpin this. Well-powered longitudinal studies that examine how host genetics is associated with varying CST, mucosal immune markers, and BV trajectories could be informative to understanding this variability in pathology within non-optimal CSTs. Additionally studies are needed to explore the potential long range regulation of these SNPs on genes, as well as evaluate for expression or methylation quantitative trait loci associations.\u003c/p\u003e \u003cp\u003eComplex traits are polygenic, and our analysis of previously reported loci identified multiple SNPs across numerous genetic loci with Bonferroni corrected significance. Several SNPs in the \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eMBL2\u003c/span\u003e region were significantly associated with \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eL. iners\u003c/span\u003e, \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eG. vaginalis\u003c/span\u003e, and CST. Kalia et al. studied these previously reported \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eMBL2\u003c/span\u003e SNPs in association with BV in women in India due to associations between mannose binding lectin (MBL) insufficiency and increased susceptibility to infectious diseases [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Among Brazilian women, a specific \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eMBL2\u003c/span\u003e polymorphism was associated with increased odds of recurrent BV compared to controls [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], though a study among Italian women that screened for three specific \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eMBL2\u003c/span\u003e SNPs found no differences for women with recurrent BV as compared to controls [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The relevance of this gene may be population specific or subject to interaction with other factors such as the prevalence of co-infections (e.g., HSV-2, HIV), sexual exposures (e.g., partner circumcision status, multiple sex partners, condom use), or non-sexual factors (e.g., cigarette smoking, intravaginal practices). Additionally, we identified SNPs in IL-1RN (CST), IL-5 (Shannon), and IL5RA (\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eL. iners\u003c/span\u003e, Shannon). IL-1RN (the gene for interleukin 1 receptor agonist, IL-1RA) inhibits the inflammatory IL-1 cytokines, IL-1α, and IL-1β. In a study of 62 Italian women, compared to women with Nugent score 0\u0026ndash;3, women with BV (Nugent score 7\u0026ndash;10) had increased IL-1RA, and increased inflammatory IL-5 was associated with decreased \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eLactobacillus\u003c/span\u003e [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In candidate gene analysis, Si et al. targeted genetic variants of IL-5 finding association with increased abundances of various \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ePrevotella\u003c/span\u003e [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Our findings further these studies by analyzing genetic factors and vaginal microbiome traits in a novel population and by demonstrating trans-ethnic associations for these previously identified loci.\u003c/p\u003e \u003cp\u003eIn pathway analysis, GPCR pathways were identified with \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eL. crispatus\u003c/span\u003e, \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eG. vaginalis\u003c/span\u003e, and CST, and Class B/2 (secretin family receptors) within the GPCR family were identified with Shannon diversity index and CST. GPCRs play a significant role in intracellular signaling in response to a broad range of stimuli (e.g., hormones, neurotransmitters, proteins, etc.) and across a wide range of functions (e.g., growth, nutrition requirements, response to disease, etc.) [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. This likely includes vaginal microbiome modulation, and variation in GPCR signaling may related to variations in innate immune response. LL-37 is elevated in women with BV and in an \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eex vivo\u003c/span\u003e endocervical model, after application of a GPCR inhibitor, LL-37 mediated induction of IL-8 production was inhibited [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]; this is relevant given that IL-8 is often elevated in women with BV [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. In analyses of previously reported SNPs, we found SNPs in the IL-8 gene region were associated with Shannon diversity index and CST. In an experimental study, Mares et al. demonstrate that application of CVL from women with BV induced higher levels of IL-8 and NFkappaB in human monocytes than CVL from women without BV [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Among women in the CAPRISA 004 trial, those with vaginal CST-IV had increased mucosal inflammation (including elevated IL-8) and increased risk of HIV seroconversion [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The effects of variation in GPCR signaling on innate immune response may extend to other outcomes. Among Dutch women, GWAS and pathway analysis found that genes encoding GPCR signaling were enriched for 71 \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eChlamydia trachomatis\u003c/span\u003e seropositive women compared to 169 control women [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. GPCR signaling encompasses a broad range of actions, but in conjunction with our pathway results implicating IL-8 and TLRs, and other studies showing potential roles for GPCR in cervicovaginal health, GPCR signaling merits further study as a potential pathway affecting acquisition or maintenance of vaginal \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eL. crispatus\u003c/span\u003e, CST membership, and subsequent BV status.\u003c/p\u003e \u003cp\u003eOur pathway analysis additionally linked neutrophil degranulation with \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eL. crispatus\u003c/span\u003e and \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eG. vaginalis\u003c/span\u003e. Neutrophils are effector cells in innate immunity and degranulation can have serious adverse consequences for the host due to release of damaging molecules. We are unaware of other studies linking neutrophil degranulation to the vaginal microbiome, BV, or other vaginal infections. However, myeloperoxidase (MPO) is a measure of neutrophils and is elevated in women with sexually transmitted infection (STI) [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Whether neutrophil degranulation is an important process in vaginal microbiome composition may be evaluated in subsequent studies, such as by targeting genes encoding molecules associated with this pathway (e.g., β-arrestins, Rac2) [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLastly, pathway analysis identified \u0026lsquo;MyD88:MAL (TIRAP) cascade\u0026rsquo; with \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eL. iners\u003c/span\u003e, and we identified SNPs within the \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eMyD88\u003c/span\u003e gene in relation to \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eL. iners\u003c/span\u003e and Shannon diversity index. MyD88:Mal (TIRAP) is an adaptor to MyD88, the first downstream component of TLR4 and TLR2, and part of the larger overall process for inflammatory cytokine effects [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. In pathway analysis, several TLR signaling associations were associated with \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eL. iners\u003c/span\u003e relative abundance, and in analysis of previously reported SNPs, TLR2, and TLR3 had associations with Shannon diversity index, CST, and \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eL. iners\u003c/span\u003e. As summarized in Supplementary Table\u0026nbsp;1, several investigators have found polymorphisms in TLR genes related to altered risk of BV and enrichment of BV-related bacteria. TLRs, especially TLR2 alone or in combination with TLR-1/TLR-6 and TLR-4, have been recognized for their association with BV and BV-related bacteria, as these TLRs precipitate release of pro-inflammatory cytokines and recruitment of inflammatory cells [\u003cspan additionalcitationids=\"CR44 CR45 CR46\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. As summarized by Taylor et al., TLR gene variants can lead to inadequate or excess inflammatory immune response, which can affect disease susceptibility or progression [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Additionally studies are needed to evaluate the potential biological role TLRs have on vaginal microbiome composition. Given that the microbiome is a complex trait and complex traits are pleiotropic, this may provide understanding of how TLR variants contribute to risk of BV, response to BV treatment, or other outcomes of non-optimal vaginal microbiome composition, such as adverse pregnancy outcomes. Taken together, our findings demonstrate numerous biologically relevant pathways and phenotypes associated with vaginal microbiome traits.\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eWe found substantial functional overlap in several biologically relevant innate immunity pathways. This may in part be driven by the compositionality of individual taxa. To mitigate this, we limited examination to a few traits of known importance in conjunction with comprehensive community characterization. We also confirmed numerous SNPs in close proximity to genomic loci associated with innate immunity reported in previous studies of host genetic traits associated with BV and vaginal taxa. Although we identified novel candidate regions associated with vaginal microbiome traits, additional studies are needed to replicate our findings. Evaluation of functional impact with multi-omic studies (such as gene expression, epigenetics, and fine mapping) would allow mechanistic inference and aid in elucidating regulatory elements, which could lead to translational advances in optimizing the vaginal microbiome and preventing BV and associated consequences.\u003c/p\u003e \u003c/div\u003e "},{"header":"Conclusions","content":" \u003cp\u003eGiven the multiple associations of important microbiome traits with various immune signaling pathways, the composition of the vaginal microbiome (and subsequently, BV risk) likely is influenced by host genetics through immune phenotypes. Replication studies and functional studies are needed to confirm and further elucidate understanding of how vaginal bacteria interact with the genetic make-up of the host to effect non-optimal vaginal microbiome and related outcomes. Given the co-occurrence of risk for BV, non-optimal vaginal microbiome, and HIV and STI among African and African American women, well-powered cross-national studies are needed to answer whether common variants are replicated across populations, and to identify important gene by environment interactions that inform how much risk for non-optimal vaginal microbiome may be modifiable, such as through behavioral modification or prevention or treatment of co-infections (e.g., HSV-2, HIV).\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eThis study was approved by the Ethical Review Committee of Maseno University (Kisumu, Kenya; MSU/DRPC/MUERC/00054/13; January 13, 2014), and the Institutional Review Board of the University of Illinois at Chicago (USA; 2013-0511; February 12, 2014).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStudy Design and Participants\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSubjects in this analysis were enrolled in \u003cem\u003eAfya Jozi, Afya Jamii \u003c/em\u003e(Kiswahili for \u0026ldquo;Healthy Pair, Healthy Community\u0026rdquo;), a prospective cohort study of heterosexual couples in Kisumu, Kenya. Recruitment and eligibility criteria have been previously published [48]. Briefly, we included men aged 18-35 years and their female partners aged 16 years and older, who independently confirmed a sexual relationship of at least 6 months duration. After the baseline visit, couples were scheduled for follow-up at 1 month, 6 months, and 12 months. Couples were enrolled from April 1, 2014, through June 22, 2016 and 12-month follow-up was completed June 21, 2017.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSpecimen Collection\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAt each scheduled study visit, participants underwent a standardized medical history and physical examination, followed by a personal interview to obtain socio-demographic and behavioral information. At baseline and each follow-up visit, clinicians collected vaginal swabs for assessment of BV. Gram stained slides were evaluated according to Nugent\u0026rsquo;s criteria, and a score of 7-10 was defined as BV following clinical recommendations [49]. Vaginal swab collection was followed by collection of cervicovaginal lavage (CVL) in 10 ml sterile water. Aliquots of 2mL were stored at -80\u0026ordm; until shipment to Chicago for processing.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eVaginal Microbiome Characterization\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe used the vaginal microbiome as measured from the baseline visit for this analysis, because antimicrobial treatment was provided for BV and other cervicovaginal infections which may confound subsequent vaginal microbiome observations. DNA extraction, library preparation and sequencing were performed at the University of Illinois at Chicago Sequencing Core (UICSQC). DNA was extracted from CVL specimens using a PowerFecal DNA kit (Qiagen). A two-stage PCR protocol was used to amplify the V3-V4 variable region of bacterial 16S rRNA genes [50]. Illumina MiSeq was used to sequence the amplicons after pooling, implementing V3 chemistry (600 cycles). Quality control and taxonomic annotation were conducted by University of Maryland Institute for Genomic Science (UMD IGS) following previously published protocol [51]. Community state types (CSTs) were determined by hierarchical clustering of relative abundances of taxa, using VALENCIA algorithm implemented by UMD IGS, which uses a distance-based metric to classify each sample to a CST based on the similarity of that sample to the centroid of CSTs identified in a reference set [52]. Raw sequence data files are available in the Sequence Read Archive (National Center for Biotechnology Information; BioProject identifier PRJNA516684).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eGenotyping and Quality Control\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eGenomic DNA was obtained from 200 Kenyan women using oral swabs and was extracted using QIAamp DNA blood mini kit (Qiagen). DNA extraction and isolation was performed at the Center for Population Epigenetics at Northwestern University. Study participants were genotyped using the Infinium Global Screening Array (~640,000 markers; Illumina, Inc., San Diego). The software Illumina GenomeStudio (v2.0.4, Illumina, Inc., San Diego) was used to call single nucleotide polymorphisms (SNPs) at the Genomic Facility, University of Chicago. Study participants with a genotyping call rate less than 95% were excluded from analysis as were study participants with missing vaginal microbiome traits. Due to cryptic relatedness identified during quality control, we restricted all analyses to the maximum number of unrelated individuals. Implementation of these exclusion criteria resulted in 171 study participants for analysis. SNPs with a call rate less than 95%, a minor allele frequency less than 1%, or a Hardy-Weinberg equilibrium \u003cem\u003eP\u003c/em\u003e value less than 10\u003csup\u003e-6\u003c/sup\u003e were omitted. After these exclusion criteria, 336,151 remained for further analysis.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eGenotype Imputation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe performed genotype imputation to identify additional SNPs associated with the vaginal microbiome traits that were not directly genotyped using the Luhya in Webuye, Kenya reference panel from the 1000 Genomes Project [53]. The program Shapeit2 [54] was used to phase genotypes and imputation was performed using Minimac3 [55]. Imputed genotypes were coded as allelic dosages (estimated counts ranging from 0 to 2). Low quality imputed SNPs, i.e. Rsq \u0026lt; 0.30 and MAF \u0026lt; 1%, were excluded from further analyses.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical Analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe evaluated the association between single nucleotide polymorphisms (SNPs) with five vaginal microbiome traits: (1) presence of \u003cem\u003eL. crispatus\u003c/em\u003e, relative abundances of (2) \u003cem\u003eL. iners \u003c/em\u003eand (3) \u003cem\u003eG. vaginalis\u003c/em\u003e, (4) Shannon diversity index, and (5) CST. We chose \u003cem\u003eL. crispatus\u003c/em\u003e for its known importance in vaginal microbiome health, \u003cem\u003eL. iners\u003c/em\u003e due to its predominance among \u003cem\u003eLactobacillus\u003c/em\u003e species in our sample and other African samples, and \u003cem\u003eG. vaginalis \u003c/em\u003edue to its inclusion as a morphotype in Nugent scoring and determination of BV. For alpha diversity measures, we selected Shannon diversity index, as all alpha diversity measures were highly correlated (Spearman correlations, 0.77 \u0026ndash; 0.98). Prior to analyses, the relative abundance of \u003cem\u003eL. iners\u003c/em\u003e and Shannon diversity index were inverse log-transformed to approximate a more normal distribution (\u003cstrong\u003eSupplemental Figure 2\u003c/strong\u003e). As transformation did not lead to normal approximation, the relative abundance of \u003cem\u003eG. vaginalis \u003c/em\u003ewas analyzed by quartile. Given the infrequency of \u003cem\u003eL. crispatus\u003c/em\u003e (present in 24% of samples) we analyzed it as presence vs. absence. Of 171 subjects in the analysis, 168 (98%) baseline vaginal microbial communities were classified as CST-I (n=14; 0% with BV), CST-III (n=77; 5.2% with BV), or CST-IV (n=77; 43% with BV). There were three outliers (n=2 with CST-II, n=1 with CST-V), and these observations were excluded from CST analyses. BV was not analyzed as a separate outcome because it was collinear with CST. We analyzed CST as a linear outcome given the ordinal nature of BV risk, and to meet parameters for statistical software.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrincipal components of genetic ancestry were generated using the program EIGENSOFT [56] and the first three principal components were retained and included as covariates. Quantile-quantile (Q-Q) plots were generated for each trait to visualize test statistics and the genomic control inflation factors were calculated. We used PLINK (v1.90) [57] to test the associations between \u003cem\u003eL. iners\u003c/em\u003e, \u003cem\u003eG. vaginalis\u003c/em\u003e, Shannon diversity index, and CST with SNPs using linear regression, and association between \u003cem\u003eL. crispatus \u003c/em\u003eand SNPs using logistic regression, adjusting for age and principal components. We assumed an additive genetic effects model for all analyses. To account for genotype uncertainty, the allelic dosages from imputed SNPs were analyzed using Mach2QTL for linear regression and Mach2DAT for logistic regression (see Web Resources). SNPs with a \u003cem\u003eP\u003c/em\u003e value less than 1.49\u0026times;10\u003csup\u003e-7\u003c/sup\u003e (0.05/336,151) were declared genome-wide significant. The software R (3.5.0) [58] and LocusZoom [59] (hg19/1000 Genomes AFR) were used for graphing.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePathway and Pleiotropy Analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe performed pathway and pleiotropy analysis using SKAT-O [60] and WebGestalt [61] to examine the combined genetic effects on the underlying biological mechanisms influencing the vaginal microbiome traits. We mapped all directly genotyped SNPs to autosomal genes based on the genomic positions of the GRCh37/hg19 assembly and included \u0026plusmn;20 kb gene boundary to capture proximal regulatory and functional elements that contribute to gene regulation. Gene-set associations were performed using SKAT-O, adjusting for age and the first three principal components. Over-representation analyses of pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome) and diseases / phenotypes (DisGeNET, GLAD4U, Online Mendelian Inheritance in Man (OMIM), and Human Phenotype Ontology) was analyzed using WebGestalt. Pathways, diseases, and phenotypes with a false discovery rate (FDR) \u003cem\u003eP\u003c/em\u003e value \u0026lt; 0.05 after Benjamini-Hochberg multiple testing adjustment were declared significant. The top five pathways and diseases / phenotypes from WebGestalt are reported.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cbr /\u003e \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eWeb Resources\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eMach2DAT, \u003ca href=\"http://csg.sph.umich.edu/abecasis/MACH/download/\"\u003ehttp://csg.sph.umich.edu/abecasis/MACH/download/\u003c/a\u003e\u003c/p\u003e\n\u003cp\u003eMach2QTL, \u003ca href=\"http://csg.sph.umich.edu/abecasis/MACH/download/\"\u003ehttp://csg.sph.umich.edu/abecasis/MACH/download/\u003c/a\u003e\u003c/p\u003e"},{"header":"Supplemental Figure Information","content":"\u003cp\u003e\u003cstrong\u003eSupplemental Figure \u003c/strong\u003e\u003cstrong\u003e1A-1E. Q-Q plots for five vaginal microbiome traits measured in 171 Kenyan women\u003c/strong\u003e\u003cstrong\u003e. \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLegend: Inspection of Q-Q plots for each microbiome trait evaluated indicate proper control of population stratification.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplemental Figure 2A-E.\u0026nbsp; Regional conditional association plots of the top genomic loci associated with vaginal microbiome traits.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLegend: P values (\u0026minus;log10) of the GWAS (solid circle) on the y-axis are plotted against the genomic positions of each SNP on the x-axis for each microbiome trait. Genes in the region are shown below. The linkage disequilibrium (LD) values (r\u003csup\u003e2\u003c/sup\u003e) between the lead SNP and the other SNPs are indicated in different colors.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e: This study was approved by the Ethical Review Committee of Maseno University (Kisumu, Kenya; MSU/DRPC/MUERC/00054/13; January 13, 2014), and the Institutional Review Board of the University of Illinois at Chicago (USA; 2013-0511; February 12, 2014). Written informed consent was obtained from all participants in their language of choice (English, DhoLuo, or Kiswahili).\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e: The authors declare that they have no competing interests\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This study was supported by grant number R01-AI110369 (PI: Mehta) from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of Microbiology, and by the National Cancer Institute of the National Institutes of Health under award number U54CA221205 (MPI: Hou, Murphy). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e:\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eSDM\u003c/strong\u003e: Obtained funding; study conceptualization and design; drafted manuscript.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eDN\u003c/strong\u003e: Design and implementation of statistical analysis approach; visualization; critical review and revision of manuscript\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eFO\u003c/strong\u003e: Study oversight and management to ensure integrity to protocols; critical review and revision of manuscript\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eSJG\u003c/strong\u003e: Development and oversight of protocols for amplicon sequencing; microbiologic analyses and interpretation; critical review and revision of manuscript\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eWA\u003c/strong\u003e: Development, implementation, and oversight of laboratory protocols in Kenya; acquisition of data; microbiologic analyses and interpretation; critical review and revision of manuscript.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eAL\u003c/strong\u003e: Critical review and revision of manuscript.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eYZ\u003c/strong\u003e: Design and interpretation of statistical analysis approach; critical review and revision of manuscript\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eLH\u003c/strong\u003e: Selection of GWAS methods; design of analysis; interpretation of results; critical review and revision of manuscript.\u003c/li\u003e\n\u003c/ul\u003e\n\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e Not applicable\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eAuthors' information (optional)\u003c/strong\u003e: Not applicable\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTorrone EA, Morrison CS, Chen PL, Kwok C, Francis SC, Hayes RJ, Looker KJ, McCormack S, McGrath N, van de Wijgert J, et al: \u003cstrong\u003ePrevalence of sexually transmitted infections and bacterial vaginosis among women in sub-Saharan Africa: An individual participant data meta-analysis of 18 HIV prevention studies.\u003c/strong\u003e \u003cem\u003ePLoS Med \u003c/em\u003e2018, \u003cstrong\u003e15:\u003c/strong\u003ee1002511.\u003c/li\u003e\n\u003cli\u003eAtashili J, Poole C, Ndumbe PM, Adimora AA, Smith JS: \u003cstrong\u003eBacterial vaginosis and HIV acquisition: a meta-analysis of published studies.\u003c/strong\u003e \u003cem\u003eAIDS \u003c/em\u003e2008, \u003cstrong\u003e22:\u003c/strong\u003e1493-1501.\u003c/li\u003e\n\u003cli\u003eLewis FM, Bernstein KT, Aral SO: \u003cstrong\u003eVaginal Microbiome and Its Relationship to Behavior, Sexual Health, and Sexually 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Baseline participant characteristics and vaginal microbiome composition overall and stratified by community state type*.\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse: collapse; border: none;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eTotal, N=171\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003en (%)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eCST I, N=14\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003en (%)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eCST-III, N=77\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003en (%)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eCST-IV, N=77\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003en (%)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eMedian age in years (IQR)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e22 (20-25)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e24.5 (19-28)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e23 (20-25)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e22 (20-25)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eHIV status\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp; Negative\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp; Positive\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp; Missing\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e152 (89.9)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e17 (10.1)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e2\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e14 (100)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e70 (92.1)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e6 (7.9)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e65 (85.5)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e11 (14.5)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eHSV-2 status\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp; Negative\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp; Positive\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e81 (47.4)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e90 (52.6)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e12 (85.7)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp; 2 (14.3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e39 (50.6)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e38 (49.4)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e28 (36.4)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e49 (63.6)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eCircumcised male sex partner\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e91 (53.2)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e6 (42.9)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e43 (55.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e40 (52.0)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eBV (Nugent score 7-10) at baseline\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e37 (21.6)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0 (0)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e4 (5.2)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e33 (42.9)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eProportion of visits with BV over follow-up \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp; 0%\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp; 25%\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp; \u0026gt;25%-50%\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp; \u0026gt;50%-75%\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp; 100%\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e89 (52.1)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e22 (12.9)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e33 (20.2)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e19 (11.1)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e8 (4.7)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e14 (100)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e49 (63.6)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e10 (13.0)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e11 (14.3)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e7 (9.1)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e25 (32.5)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e11 (14.3)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e21 (27.3)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e12 (15.5)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e8 (10.4)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ePresence of \u003cem\u003eL. crispatus \u003c/em\u003eat baseline \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e42 (24.6)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e14 (100)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e22 (28.6)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e6 (7.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; Mean RA \u003cem\u003eL. crispatus \u003c/em\u003eif \u003cbr /\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; present (SD)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e28.2 (35.3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e72.5 (21.6)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e7.71 (13.0)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.21 (0.34)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ePresence of \u003cem\u003eL. iners \u003c/em\u003eat baseline \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e142 (83.0)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e5 (35.7)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e77 (100)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e58 (75.3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; Mean RA \u003cem\u003eL. iners \u003c/em\u003eif \u003cbr /\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; present (SD)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e44.8 (42.4)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1.84 (3.24)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e80.3 (23.2)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e2.99 (5.11)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ePresence of \u003cem\u003eG. vaginalis \u003c/em\u003eat baseline \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e129 (75.4)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e7 (50.0)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e46 (59.7)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e73 (94.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; Mean RA \u003cem\u003eG. vaginalis \u003c/em\u003eif \u003cbr /\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; present (SD)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e23.1 (24.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e20.9 (15.0)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e6.81 (10.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e33.7 (26.7)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: .3in;\"\u003e\n\u003ctd style=\"width: 143.75pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eMedian Shannon diversity index (IQR)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.94 \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e(0.30 \u0026ndash; 1.82)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.80 \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e(0.33 \u0026ndash; 0.98)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.5pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e0.34 \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e(0.16 \u0026ndash; 0.83)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.25pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: .3in;\" width=\"114\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e1.84\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e(1.20 \u0026ndash; 2.17)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eIQR = Interquartile range; BV = Bacterial vaginosis; RA = Relative abundance; SD = Standard Deviation\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e* CST-IV combined sub-types A (n=9), B (n=62), and C (n=6). Three observations (n=2 with CST-II, n=1 with CST-V) are not included in this table. \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 11.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eTable 2. Top single nucleotide polymorphisms associated with five vaginal microbiome traits. \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width: 667.2pt; border-collapse: collapse;\" width=\"890\"\u003e\n\u003ctbody\u003e\n\u003ctr style=\"height: 21.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 21.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 21.55pt;\" width=\"106\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eSNP\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 21.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eChr\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 21.55pt;\" width=\"94\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ePosition\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 21.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eGene\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 21.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eA1/A2\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 21.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eMAF\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 21.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: Symbol; color: black;\"\u003eb\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 21.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eP\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\n\u003cp\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eL. crispatus\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers73330467\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e5\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e125694420\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black; background: white;\"\u003eLOC101927488\u003c/span\u003e\u003c/em\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e-GRAMD2B\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eG/T\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.07\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e11.58\u003csup\u003e*\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e4.79E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\n\u003cp\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eL. iners\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers527430\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e1\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e47918821\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eFOXD2-\u003cspan style=\"background: white;\"\u003eTRABD2B\u003c/span\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eA/G\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e1.05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e6.98E-07\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers77007265\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e2\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e31384829\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eGALNT14-CAPN14\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eC/A\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.08\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e-0.93\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e2.07E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers17010778\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e2\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e31384974\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eGALNT14-CAPN14\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eC/T\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e-1.00\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e3.60E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers12221275\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e10\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e122972398\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black; background: white;\"\u003eWDR11-FGFR2\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eA/C\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.01\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e2.22\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e6.95E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\n\u003cp\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eG. vaginalis\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers1229660\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e7\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e26437429\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eSNX10-\u003cspan style=\"background: white;\"\u003eLOC441204\u003c/span\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eC/T\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.10\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e-0.99\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e4.65E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers10414170\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e19\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e57246309\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black; background: white;\"\u003eZNF835-ZIM2-AS1\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eC/A\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.30\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e-0.62\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e6.56E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eShannon Diversity Index\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers7632135\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e3\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e154455745\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black; background: white;\"\u003eGPR149-MME\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eG/A\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.24\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e-0.59\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e4.37E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers3097137\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e5\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e73330562\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black; background: white;\"\u003eARHGEF28\u003c/span\u003e\u003c/em\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e-\u003cspan style=\"background: white;\"\u003eLINC01335\u003c/span\u003e\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eA/G\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.20\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.56\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e4.25E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers112627544\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e7\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e1929410\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eMAD1L1\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eT/G\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.42\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e-0.47\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e9.04E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers6970796\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e7\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e1947895\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eMAD1L1\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eT/C\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.36\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e-0.50\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e2.25E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers56952063\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e14\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e95107145\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black; background: white;\"\u003eSERPINA13P\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eC/T\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.08\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e-0.90\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e9.65E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers972741\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e16\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e25468083\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black; background: white;\"\u003eZKSCAN2-HS3ST4\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eA/G\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.19\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.66\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e8.52E-07\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 215.9pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"288\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eCommunity State Type \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 71.2pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"95\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 54.2pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers419816\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e5\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e52571758\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eLOC257396-FST\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eC/T\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.13\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.45\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e9.99E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers1929353\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e9\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e3759975\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black; background: white;\"\u003eRFX3-AS1-GLIS3\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eG/A\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.24\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.35\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e9.51E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.55pt;\"\u003e\n\u003ctd style=\"width: 136.4pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 79.5pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"106\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003ers2302902\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 38.95pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"52\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e12\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 70.8pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" width=\"94\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e96617304\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 149.85pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"200\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eELK3\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 44.4pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"59\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eT/C\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 37.1pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"49\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.20\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.8pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"72\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e0.41\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.6pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.55pt;\" colspan=\"2\" width=\"74\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e3.09E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"border: none; padding: 0in 0in 0in 0in;\" width=\"1\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"border: none;\" width=\"182\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"106\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"52\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"94\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"199\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"59\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"49\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"71\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"73\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"border: none;\" width=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eSNP, Single nucleotide polymorphism; Chr, Chromosome; A1/A2, allele 1 / allele 2; MAF, Minor allele frequency.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003eSNPs with a \u003cem\u003eP\u003c/em\u003e \u0026lt;1\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: Symbol; color: black;\"\u003e\u0026acute;\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e10\u003csup\u003e-5\u003c/sup\u003e for each trait are included in the table. Gene name is in boldface if the SNP is located within the gene.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e*\u003c/span\u003e\u003c/sup\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e Reported as odds ratio\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eTable 3. Results of pathway analysis: Top KEGG and Reactome pathways associated \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ewith vaginal microbiome traits.\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width: 639.45pt; border-collapse: collapse; border: none;\" width=\"853\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eTrait\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003ePathway\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eObserved/Total Genes\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eP\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eAdjusted \u003cem\u003eP\u003c/em\u003e\u003csup\u003e*\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cem\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eL. crispatus\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eMetabolism of amino acids and derivatives\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e29/370\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e7.27E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.10E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eGPCR ligand binding\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e32/457\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e2.46E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.37E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003ePCP/CE pathway\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e11/92\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.50E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e3.97E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eBeta-catenin independent WNT signaling\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e14/145\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e2.04E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e4.72E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eNeutrophil degranulation\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e30/479\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e3.12E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e5.31E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cem\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eL. iners\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eToll-like receptor cascades\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e17/155\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e8.41E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e9.76E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eMyD88:MAL(TIRAP) cascade initiated on plasma membrane\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e13/95\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e8.82E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e9.76E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eToll like receptor TLR6:TLR2 cascade\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e13/95\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e8.82E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e9.76E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eToll like receptor TLR1:TLR2 cascade\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e13/98\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.25E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e9.76E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eToll like receptor 2 (TLR2) cascade\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e13/98\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.25E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e9.76E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cem\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eG. vaginalis\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cem\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eSignaling by GPCR\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e66/1162\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e5.35E-07\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.46E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eGPCR downstream signaling\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e63/1100\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e7.45E-07\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.46E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eNeutrophil degranulation\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e29/479\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e3.11E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e2.44E-01\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eG alpha (s) signaling events\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e31/536\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e4.29E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e2.80E-01\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eFormation of the cornified envelope\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e12/129\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e5.23E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e2.93E-01\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 418.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"2\" width=\"558\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eShannon Diversity Index\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eClass B/2 (secretin family receptors)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e12/95\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.89E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e3.71E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eRNA polymerase II transcription\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e62/1292\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e6.53E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e5.12E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eGene expression (transcription)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e66/1430\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.19E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e6.52E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eNeuronal system\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e24/368\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.99E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e6.52E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eCleavage of growing transcript in the termination region\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e8/67\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e6.80E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e9.52E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 418.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"2\" width=\"558\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eCommunity State Type\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eHuman T-cell leukemia virus 1 infection\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e20/255\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e8.77E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e9.30E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eClass B/2 (secretin family receptors)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e11/95\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.23E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.06E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eGPCR ligand binding\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e29/457\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.25E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.06E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003ePost-translational modification: synthesis of GPI-anchored proteins\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e10/92\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e4.17E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.89E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 76.5pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 4.75in; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"456\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eTransmission across chemical synapses\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.95pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"115\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e17/227\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e4.95E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 67.5pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"90\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e2.12E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"tab-stops: 376.8pt;\"\u003e\u003csup\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e*\u003c/span\u003e\u003c/sup\u003e\u003cem\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eP\u003c/span\u003e\u003c/em\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e-values are Benjamini-Hochberg adjusted\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 11.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eTable 4. Results of pleiotropy analysis: Top phenotypes associated \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003ewith vaginal microbiome traits.\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse: collapse; border: none;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eTrait\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003ePhenotype\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eObserved/Total Genes\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cem\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eP\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eAdjusted \u003cem\u003eP\u003c/em\u003e\u003csup\u003e*\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cem\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eL. crispatus\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eBacterial infections\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e23/260\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e9.25E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.10E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eMeckel syndrome (MKS)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e17/164\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.78E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.37E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eHypertension, pulmonary\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e15/137\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e2.88E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.37E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eVaricose veins\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e11/79\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e3.64E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.45E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eGram-positive bacterial infections\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e17/181\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e6.29E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e2.15E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 5.8pt;\"\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cem\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eL. iners\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"84\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eAutosomal dominant inheritance\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e72/1403\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e3.17E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.78E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eGrowth abnormality\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e88/1822\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e3.89E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.91E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eAbnormality of the cardiovascular system\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e86/1796\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e6.49E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e2.83E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eAplasia/hypoplasia involving the vertebral column\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e8/55\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e3.08E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e8.05E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eAbnormality of hair density\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e20/267\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e3.35E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e8.05E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 5.8pt;\"\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cem\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eG. vaginalis\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"84\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003ePancreatic neoplasm\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e11/88\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e6.51E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e8.52E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eCarcinoma, pancreatic ductal\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e13/139\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e2.95E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e2.44E-01\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003ePancreatic neoplasms\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e19/281\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e9.08E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e3.56E-01\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eNeoplasm of the endocrine system\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e9/89\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.42E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e4.11E-01\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eThyroid neoplasms\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e13/165\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.48E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e4.11E-01\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 5.8pt;\"\u003e\n\u003ctd style=\"width: 328.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" colspan=\"2\" width=\"438\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eShannon Diversity Index\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"84\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eAbnormality of the female genitalia\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e33/505\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.31E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e3.71E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eAbnormality of female internal genitalia\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e29/444\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e4.38E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e5.12E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eAbnormal internal genitalia\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e30/473\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e5.57E-05\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e5.12E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eAbnormality of the uterus\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e15/176\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.92E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e6.52E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eAbnormality of the ovary\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e16/196\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.96E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e6.52E-02\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 5.8pt;\"\u003e\n\u003ctd style=\"width: 328.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" colspan=\"2\" width=\"438\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003eCommunity State Type\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"192\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"84\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 5.8pt;\" width=\"150\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eSerotonin syndrome\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e23/134\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.18E-11\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e4.39E-08\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eAbnormality of the integument\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e99/1920\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e5.16E-08\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.01E-04\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eAutosomal dominant inheritance\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e74/1403\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.33E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.50E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003ePrader-Willi syndrome\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e20/195\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.70E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.50E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 83.55pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 244.95pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"327\"\u003e\n\u003cp\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003eAbnormality of the skin\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 2.0in; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"192\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e80/1572\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.92E-06\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-family: 'Times New Roman',serif; color: black;\"\u003e1.50E-03\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e*\u003c/span\u003e\u003c/sup\u003e\u003cem\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eP\u003c/span\u003e\u003c/em\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e-values are Benjamini-Hochberg adjusted\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eSupplemental Table 1. Excel File. Details of Candidate Gene Analysis Findings\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Vaginal microbiome, Vaginal microbiota, Bacterial vaginosis, L. crispatus, L. iners, G. vaginalis, Shannon diversity index, community state type, genome wide association study, pathway analysis, toll-like receptors, innate immune response, Kenya","lastPublishedDoi":"10.21203/rs.3.rs-17153/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-17153/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground Women with vaginal microbial community state types (CST) with high diversity and a paucity of Lactobacillus crispatus have increased risk of HIV acquisition. Identifying host genetic factors associated with the vaginal microbial composition may aid in elucidating the biological mechanisms regulating these microbial traits and inter-individual variations in associated diseases. \u003c/p\u003e\u003cp\u003eMethods We conducted genome-wide associations studies (GWASs) on vaginal microbiome traits on 171 Kenyan women. Study participants were genotyped using the Infinium Global Screening Array and 16S rRNA gene amplicon sequencing was performed to characterize the vaginal microbiome. Linear and logistic regression were performed, adjusting for age and principal components of genetic ancestry, to evaluate the association between L. crispatus, L. iners, G. vaginalis, Shannon diversity index, and CST with host genetic single nucleotide polymorphisms (SNPs). Pathway enrichment analyses were performed to identify biological processes putatively associated with the vaginal microbiome traits. \u003c/p\u003e\u003cp\u003eResults At baseline, the median age of study participants was 22 years (IQR: 22 – 25) with 22% having Bacterial vaginosis (Nugent score 7-10). L. crispatus and L. iners were present in 24% and 83% of samples with a mean relative abundance of 31% and 45%, respectively. The most significant SNPs associated were: rs73330467 located between LOC101927488-GRAMD2B ( P =4.79x10 -6 ) for L. crispatus ; rs527430 in the FOXD2-TRABD2B ( P =6.98x10 -7 ) region for L. iners ; rs1229660 in the SNX10-LOC441204 ( P =4.65x10 -6 ) region for G. vaginalis; rs972741 in the ZKSCAN2-HS3ST4 ( P =8.52x10 -7 ) region for Shannon diversity index; and rs2302902 in ELK3 ( P =3.09x10 -6 ) for CST. During pathway enrichment analysis, Toll-like receptors, cytokine production, and other components of innate immune response were associated with L. crispatus, L. iners, and CST. Multiple genomic loci were replicated, including IL-8 (Shannon, CST), TIRAP ( L. iners , Shannon), TLR2 (Shannon, CST), MBL2 ( L. iners , G. vaginalis , CST), and MYD88 ( L. iners, Shannon). \u003c/p\u003e\u003cp\u003eConclusions We identified numerous genetic loci on several pathways related to host immunity and infection that were associated with vaginal microbiome traits, providing insight into potential host genetic influences on vaginal microbiome composition. This new information should guide larger longitudinal studies, with genetic and functional comparison across microbiome sites within individuals, and across populations.\u003c/p\u003e","manuscriptTitle":"Host Genetic Determinants of the Vaginal Microbiome in Kenyan Women","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-03-13 15:03:05","doi":"10.21203/rs.3.rs-17153/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cac6ca3f-c42a-42b4-950a-2015a9b016ee","owner":[],"postedDate":"March 13th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":69775,"name":"General Microbiology"}],"tags":[],"updatedAt":"","versionOfRecord":[],"versionCreatedAt":"2020-03-13 15:03:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-17153","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-17153","identity":"rs-17153","version":["v1"]},"buildId":"wLkW0s4AflPzk-lpfg-fK","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}