Psoriasis and Pulmonary Function - Unveiling Genetic Connections

Psoriasis and Pulmonary Function - Unveiling Genetic Connections | 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Psoriasis and Pulmonary Function - Unveiling Genetic Connections Kazuya Tanimura, Melinda Aldrich, James Jaworski, Jinchuan Xing, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4474529/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 Psoriasis, an immune-mediated skin disease characterized by erythematous plaques, is often associated with chronic lung diseases that impair pulmonary function. To investigate a potential genetic link between psoriasis and pulmonary function, we analyzed 63 previously reported psoriasis-associated single nucleotide polymorphisms (SNPs) for their associations with both psoriasis and pulmonary function measurements using data from the UK Biobank (UKBB) and Vanderbilt University Medical Center Biobank (BioVU). Our results confirm significant associations of specific SNPs with both the risk of psoriasis and changes in pulmonary function. Notably, the minor alleles of rs17716942 and rs8016947 were linked to a lower risk of psoriasis and improved pulmonary function across both biobank cohorts. These findings highlight potential genetic intersections involving immune regulation and inflammatory responses, mediated by genes such as IFIH1, GCA, and NFKBIA, which may underlie the observed "skin-lung axis" in psoriatic patients. Figures Figure 1 Main Text Psoriasis, an immune-mediated skin disease affecting 2% of the world’s population, characterized by well-demarcated, erythematous plaques with hyperkeratinization[1]. Beyond its cutaneous manifestations, psoriasis is often associated with chronic inflammatory diseases involving the cardiovascular, respiratory, and gastrointestinal systems. Several genome-wide association studies (GWAS) identified genetic loci implicated in psoriasis that alter inflammatory pathways, including IL-23/IL-17, NFKB, and Type 1 interferon signaling, skin barrier integrity, and antigen presentation[2]. Patients with psoriasis exhibit a higher prevalence of pulmonary comorbidities, such as chronic obstructive pulmonary disease (COPD), asthma, and pneumonia, compared to individuals without psoriasis [3-5]. The presence of psoriasis is linked to an increased rate of respiratory-related mortality [6], suggesting that specific pulmonary manifestations in those with psoriasis may predict a poor prognosis. Previous analyses have demonstrated an elevated risk of respiratory failure accompanied by asthma and airflow limitation, in psoriatic individuals[7]. Consequently, we propose that certain genetic variants linked to psoriasis may adversely affect lung function. This hypothesis was explored using data from two independent sources i.e., the UK Biobank (UKBB) and the Vanderbilt University Medical Center Biobank (BioVU). The UKBB is a large population-based database including biomedical, medical, and genetic information from approximately 500,000 participants [8]. Genome-wide genotyping was performed using the UK Biobank Axiom Array. Approximately 850,000 markers were included, and the imputation was performed using IMPUTE4 [9]. Among the 63 previously reported psoriasis-associated single nucleotide polymorphisms (SNPs) from the European origin populations[10-14], we identified loci significantly associated with a self-reported diagnosis of psoriasis in White individuals controlling for age and sex using the UKBB database. If the originally reported psoriasis-associated SNPs were not available in the UKBB database, we analyzed their proxy SNPs with R2 >0.5 identified using LDproxy Tool (https://ldlink.nih.gov/?tab=ldproxy). We then determined whether the identified loci were significantly associated with pulmonary function (forced expiratory volume in one second [FEV 1 ] in litter, forced vital capacity [FVC] in litter, and FEV 1 /FVC ratio). To validate our findings, we used data from BioVU[15]. BioVU participants were previously genotyped using the Illumina MEGA-Ex array and imputed with PLINK using the 1000 Genomes Project as a reference dataset. We identified White individuals participating in BioVU with available pulmonary function data and genome-wide genotyping data. Using the GENESIS software package[16], we conducted linear regression analyses, adjusting for age, age 2 , sex, smoking status (never/ever), and height. We used Benjamini and Hochberg false discovery rate (FDR) method to highlight the genes that remain statistically significant after multiple comparisons in each cohort [17]. FDR adjusted q-values were calculated and q<0.05 was considered significant. Our analysis included 346,572 participants from the UKBB and 2,189 from BioVU. Of the 63 previously reported psoriasis-associated SNPs, 53 SNPs including 28 proxy SNPs were available for analysis in the UKBB. We confirmed that 31 of these 53 SNPs were significantly associated with a diagnosis of psoriasis in the UKBB participants (15 with higher risk and 16 with lower risk of psoriasis, Table E1). Among these 31 SNPs, 16 were significantly associated with FEV 1 , 14 were associated with FVC, and 5 were associated with FEV 1 /FVC (Table 1, 2, and Table E2). To validate these findings, we used data from BioVU. Genotyping data on 27 of the 31 psoriasis-associated SNPs studied in the UKBB were available. The minor allele of rs8016947 (T) was confirmed to be significant for a lower risk for psoriasis and higher FEV 1 (minor allele frequency (MAF) 0.435, beta 0.029, standard error (SE) 0.009, q=0.001 in the UKBB; MAF 0.435, beta 0.072, SE 0.021, q=0.001 in BioVU). The minor alleles of rs17716942 (C) and rs8016947 (T) were significant for a lower risk for psoriasis and higher FVC (For rs17716942, MAF 0.132, beta 0.174, SE 0.068, q=0.010 in the UKBB; MAF 0.145, beta 0.075, SE 0.034, q=0.025 in BioVU. For rs8016947, beta 0.040, SE 0.011, q<0.001 in the UKBB; beta 0.067, SE 0.024, q=0.005 in BioVU) (Figure 1). Among 5 SNPs significantly associated with FEV 1 /FVC in the UKBB, none of these SNPs were statistically significant in BioVU. The present analysis revealed that the minor alleles of rs17716942 and rs8016947 were the unique SNPs significantly associated with a lower risk of psoriasis and higher FEV 1 and FVC in the two different cohort of UKBB and BioVU. The SNP rs17716942 is located in the Potassium Voltage-Gated Channel Subfamily H Member 7 ( KCNH7 ) gene and multiple proxy SNPs with high linkage disequilibrium (LD) are located in the surrounding region. Genes such as the Interferon Induced With Helicase C Domain 1 gene ( IFIH1 ) and Grancalcin gene ( GCA ) are located in the associated region[18]. Polymorphisms in this IFIH1 - GCA - KCNH7 locus are known to be associated with multiple sclerosis risk[19]. KCNH7 is primarily expressed in the brain tissue[20] and its polymorphisms are reportedly associated with the treatment response of schizophrenia[21]. IFIH1 encodes the melanoma differentiation associated protein 5 (MDA5) which acts as a key intracellular sensor of viral RNA and triggers the innate immune response. The loss-of-function variants of the gene is reported to be associated with the development of very early onset Inflammatory bowel disease[22]. GCA is a protein coding gene that encodes grancalcin. Grancalcin is mainly expressed in neutrophils and monocytes/macrophages and grancalcin deficient neutrophils are reported to be impaired in adhesion process[23]. Since KCNH7 is expressed at a low level in the lungs, the associated GCA and/or IFIH1 may have a main role in the pathophysiology of psoriasis and impaired lung function. The SNP rs8016947 is located near (≃40kbp) the NFKB Inhibitor Alpha gene ( NFKBIA ). NFKBIA is one of the most common regulatory proteins of NFKB, an important regulator of inflammatory responses. Polymorphisms of NFKBIA are associated with various pulmonary diseases including atopic asthma, invasive pneumococcal disease, and trauma-associated acute lung injury[24-26]. Accordingly, there may be a potential genetic link between psoriasis and pulmonary comorbidities in altered inflammatory pathways, such as the innate virus response, the neutrophil adhesion, and the abnormal regulation of excessive inflammation. It is intriguing that IFIH1 , GCA and NFKBIA regulate innate immune response because immunodysregulation responsible for the psoriasis pathogenesis may impair lung function as the systemic manifestation implicating a “skin-lung axis”. There are some limitations in the present study. First, we evaluated only known SNPs associated with psoriasis in European ancestry populations because of limited availability of other racial/ethnic groups. Therefore, these identified SNPs linked to both psoriasis and pulmonary function in the present study may not be applicable for individuals of other ancestries. The narrowed analysis would limit its generalizability. Second, some potential confounding factors, such as the severity and medications (e.g., immunosuppressants) of psoriasis were not considered due to a lack of available data. Thus, the impact of the treatment or its adverse effect cannot be excluded. Finally, these finding could be impacted by the inflating type I error due to multiple comparisons in each study cohort. In conclusion, our findings shed light on several genetic variants that bridge psoriasis and lung function, paving the way for future research into the causal relationships underlying these associations in immune-mediated skin and lung diseases. Declarations Author Contribution K.T. contributed to the study design, analyzed the data, interpreted the data, and wrote the manuscript. M.C.A. contributed to the acquisition, analysis, and interpretation of the data and edited the manuscript.J.J., J.X., and S.O. contributed to the analysis and interpretation of the data.D.C. contributed to the data analysis and edited the manuscript. S.M.N. contributed to the study design, analyzed the data, interpreted the data, and edited the manuscript.T.N. designed the study, analyzed the data, interpreted the data, and edited the manuscript.T.N. takes responsibility for the integrity of the entire project, from its inception to the manuscript’s publication. All authors reviewed the manuscript. References Christophers E. Psoriasis–epidemiology and clinical spectrum. Clin Exp Dermatol. 2001;26:314–20. Dand N, Mahil SK, Capon F, et al. Psoriasis and Genetics. Acta Derm Venereol. 2020;100:adv00030. Ungprasert P, Srivali N, Thongprayoon C. Association between psoriasis and chronic obstructive pulmonary disease: A systematic review and meta-analysis. J Dermatolog Treat. 2016;27:316–21. Fang HY, Liao WC, Lin CL, et al. Association between psoriasis and asthma: a population-based retrospective cohort analysis. Br J Dermatol. 2015;172:1066–71. Kao LT, Lee CZ, Liu SP, et al. Psoriasis and the risk of pneumonia: a population-based study. PLoS ONE. 2014;9:e116077. Colaco K, Widdifield J, Luo J, et al. Trends in mortality and cause-specific mortality among patients with psoriasis and psoriatic arthritis in Ontario, Canada. J Am Acad Dermatol. 2021;84:1302–9. Tanimura K, Nouraie SM, Chandra D, et al. Pulmonary comorbidities in psoriasis are associated with a high risk of respiratory failure. J Int Med Res. 2023;51:3000605231182881. Sudlow C, Gallacher J, Allen N, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12:e1001779. Bycroft C, Freeman C, Petkova D, et al. The UK Biobank resource with deep phenotyping and genomic data. Nature. 2018;562:203–9. Tsoi LC, Stuart PE, Tian C, et al. Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants. Nat Commun. 2017;8:15382. Tsoi LC, Spain SL, Knight J, et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet. 2012;44:1341–8. Tsoi LC, Spain SL, Ellinghaus E, et al. Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci. Nat Commun. 2015;6:7001. Bowes J, Budu-Aggrey A, Huffmeier U, et al. Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis. Nat Commun. 2015;6:6046. Yin X, Low HQ, Wang L, et al. Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility. Nat Commun. 2015;6:6916. Roden DM, Pulley JM, Basford MA, et al. Development of a large-scale de-identified DNA biobank to enable personalized medicine. Clin Pharmacol Ther. 2008;84:362–9. Gogarten SM, Sofer T, Chen H, et al. Genetic association testing using the GENESIS R/Bioconductor package. Bioinformatics. 2019;35:5346–8. Benjamini Y, Yekutieli D. The control of the false discovery rate in multiple testing under dependency. Annals Stat. 2001;29:1165–88. Machiela MJ, Chanock SJ. LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Bioinformatics. 2015;31:3555–7. Martínez A, Santiago JL, Cénit MC, et al. IFIH1-GCA-KCNH7 locus: influence on multiple sclerosis risk. Eur J Hum Genet. 2008;16:861–4. Fagerberg L, Hallström BM, Oksvold P, et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteom. 2014;13:397–406. Wang X, Su Y, Yan H, et al. Association Study of KCNH7 Polymorphisms and Individual Responses to Risperidone Treatment in Schizophrenia. Front Psychiatry. 2019;10:633. Cananzi M, Wohler E, Marzollo A, et al. IFIH1 loss-of-function variants contribute to very early-onset inflammatory bowel disease. Hum Genet. 2021;140:1299–312. Xu P, Roes J, Segal AW, et al. The role of grancalcin in adhesion of neutrophils. Cell Immunol. 2006;240:116–21. Park S-M, Chang H-S, Rhim T, et al. Association of IKBA gene polymorphisms with the development of asthma. Hum Immunol. 2010;71:1147–53. Sangil A, Arranz MJ, Güerri-Fernández R, et al. Genetic susceptibility to invasive pneumococcal disease. Infect Genet Evol. 2018;59:126–31. Meyer NJ, Daye ZJ, Rushefski M, et al. SNP-set analysis replicates acute lung injury genetic risk factors. BMC Med Genet. 2012;13:52. Tables Table 1 The associations between psoriasis susceptibility loci and FEV 1 (L) evaluated using an additive genetic model SNP Location (GRCh38.p13) The UKBB The BioVU Proxy MAF beta SE q value Proxy MAF beta SE q value rs4112788 chr1:152578800 0.341 0.021 0.01 0.042 0.350 0.016 0.022 0.47 rs41298997 chr1:206481989 rs17022427 0.237 -0.005 0.003 0.08 0.209 -0.029 0.026 0.27 rs4649203 chr1:24193430 0.266 -0.072 0.008 <0.001 0.272 0.019 0.024 0.43 rs7536201 chr1:24966593 rs4265380 0.500 -0.005 0.002 0.005 rs4265380 0.497 -0.02 0.021 0.34 rs2201841 chr1:67228519 0.311 0.001 0.002 0.54 0.314 -0.04 0.023 0.083 rs34517439 chr1:77984833 rs17391694 0.136 -0.002 0.005 0.76 0.121 -0.001 0.032 0.97 rs17716942 chr2:162404181 0.132 0.181 0.052 0.001 0.145 0.036 0.03 0.24 rs702873 chr2:60854407 0.429 0.049 0.011 <0.001 0.451 -0.003 0.021 0.89 rs10865331 chr2:62324337 0.379 -0.014 0.008 0.074 0.389 -0.015 0.021 0.48 rs20541 chr5:132660272 0.180 0.012 0.014 0.4 NA NA NA NA rs2082412 chr5:159290781 0.195 -0.027 0.009 0.002 0.209 0.018 0.026 0.5 rs27524 chr5:96766240 0.393 -0.024 0.008 0.003 0.371 -0.01 0.022 0.67 rs33980500 chr6:111592059 0.075 -0.051 0.023 0.026 0.072 0.074 0.04 0.069 rs610604 chr6:137878280 0.326 -0.064 0.008 <0.001 0.330 0.015 0.022 0.5 rs12191877 chr6:31285148 0.120 0.045 0.027 0.095 0.123 0.016 0.035 0.65 rs61871342 chr10:100278884 rs17729876 0.444 -0.003 0.002 0.13 0.413 0 0.021 0.99 rs2675662 chr10:73839369 rs2675671 0.451 0.001 0.002 0.49 rs2675671 0.423 -0.029 0.021 0.17 rs1250544 chr10:79273128 0.383 0.047 0.011 <0.001 0.369 -0.003 0.022 0.89 rs11059675 chr12:122183779 rs7972875 0.481 0.001 0.002 0.64 NA NA NA NA rs2066808 chr12:56344189 0.068 -0.085 0.007 <0.001 NA NA NA NA rs9533962 chr13:44760058 rs1415638 0.448 -0.003 0.002 0.15 rs1415638 0.411 -0.039 0.021 0.069 rs8016947 chr14:35363460 0.435 0.029 0.009 0.001 0.435 0.072 0.021 0.001 rs367569 chr16:11271643 rs243325 0.304 0.001 0.002 0.76 rs243325 0.291 -0.022 0.024 0.36 rs10782001 chr16:30931304 0.362 -0.12 0.009 <0.001 NA NA NA NA rs4795067 chr17:27779649 0.352 0.047 0.012 <0.001 0.358 -0.038 0.022 0.09 rs11652075 chr17:80205094 0.499 -0.072 0.011 <0.001 0.498 -0.024 0.021 0.27 rs545979 chr18:54293380 rs602422 0.289 0 0.002 0.87 rs602422 0.297 -0.038 0.023 0.1 rs12720356 chr19:10359299 0.097 0.032 0.126 0.8 0.089 -0.007 0.036 0.86 rs492602 chr19:48703160 0.499 0.002 0.008 0.77 0.498 0.029 0.021 0.18 rs495337 chr20:49905793 0.424 0.042 0.011 <0.001 0.417 -0.006 0.021 0.77 rs181359 chr22:21574352 0.191 -0.002 0.013 0.85 0.204 0.036 0.026 0.17 Table 2 The associations between psoriasis susceptibility loci and FVC (L) evaluated using an additive genetic model SNP Location (GRCh38.p13) UKBB BioVU Proxy MAF beta SE q value Proxy MAF beta SE q value rs4112788 chr1:152578800 0.341 0.026 0.013 0.053 0.350 0.019 0.025 0.44 rs41298997 chr1:206481989 rs17022427 0.237 -0.005 0.003 0.18 0.209 -0.021 0.029 0.46 rs4649203 chr1:24193430 0.266 -0.088 0.01 <0.001 0.272 0.033 0.026 0.21 rs7536201 chr1:24966593 rs4265380 0.500 -0.007 0.002 0.002 rs4265380 0.497 -0.026 0.023 0.26 rs2201841 chr1:67228519 0.311 0.001 0.003 0.68 0.314 -0.047 0.026 0.067 rs34517439 chr1:77984833 rs17391694 0.136 0.001 0.006 0.88 0.121 0.008 0.036 0.83 rs17716942 chr2:162404181 0.132 0.174 0.068 0.01 0.145 0.075 0.034 0.025 rs702873 chr2:60854407 0.429 0.062 0.015 <0.001 0.451 -0.018 0.023 0.43 rs10865331 chr2:62324337 0.379 -0.026 0.01 0.011 0.389 -0.018 0.024 0.45 rs20541 chr5:132660272 0.180 0.016 0.018 0.37 NA NA NA NA rs2082412 chr5:159290781 0.195 -0.022 0.011 0.051 0.209 0.05 0.029 0.083 rs27524 chr5:96766240 0.393 -0.031 0.011 0.003 0.371 -0.028 0.025 0.25 rs33980500 chr6:111592059 0.075 -0.051 0.03 0.086 0.072 0.046 0.045 0.31 rs610604 chr6:137878280 0.326 -0.077 0.01 <0.001 0.330 0.026 0.025 0.28 rs12191877 chr6:31285148 0.120 0.043 0.035 0.22 0.123 -0.006 0.039 0.88 rs61871342 chr10:100278884 rs17729876 0.444 -0.003 0.002 0.17 0.413 0.013 0.024 0.6 rs2675662 chr10:73839369 rs2675671 0.451 0.003 0.002 0.25 rs2675671 0.423 -0.006 0.024 0.81 rs1250544 chr10:79273128 0.383 0.052 0.015 <0.001 0.369 -0.008 0.024 0.73 rs11059675 chr12:122183779 rs7972875 0.481 0.003 0.002 0.21 NA NA NA NA rs2066808 chr12:56344189 0.068 -0.103 0.01 <0.001 NA NA NA NA rs9533962 chr13:44760058 rs1415638 0.448 0 0.002 0.89 rs1415638 0.411 -0.056 0.024 0.019 rs8016947 chr14:35363460 0.435 0.040 0.011 <0.001 0.435 0.067 0.024 0.005 rs367569 chr16:11271643 rs243325 0.304 -0.001 0.003 0.66 rs243325 0.291 -0.02 0.026 0.44 rs10782001 chr16:30931304 0.362 -0.153 0.011 <0.001 NA NA NA NA rs4795067 chr17:27779649 0.352 0.048 0.016 0.002 0.358 -0.015 0.025 0.56 rs11652075 chr17:80205094 0.499 -0.099 0.014 <0.001 0.498 -0.035 0.024 0.14 rs545979 chr18:54293380 rs602422 0.289 0.001 0.003 0.65 rs602422 0.297 -0.029 0.026 0.26 rs12720356 chr19:10359299 0.097 -0.052 0.164 0.75 0.089 -0.01 0.04 0.81 rs492602 chr19:48703160 0.499 -0.002 0.01 0.81 0.498 0.032 0.024 0.18 rs495337 chr20:49905793 0.424 0.057 0.014 <0.001 0.417 -0.01 0.024 0.66 rs181359 chr22:21574352 0.191 0.007 0.017 0.68 0.204 0.05 0.029 0.086 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board 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-4474529","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":310347142,"identity":"be5ae8af-59fc-4214-bb34-078c64e5aaad","order_by":0,"name":"Kazuya Tanimura","email":"","orcid":"","institution":"Nara Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kazuya","middleName":"","lastName":"Tanimura","suffix":""},{"id":310347145,"identity":"2e7789e1-58d0-41e8-9264-43be1b4bd997","order_by":1,"name":"Melinda Aldrich","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Melinda","middleName":"","lastName":"Aldrich","suffix":""},{"id":310347147,"identity":"9210dc75-feac-415d-887c-bd5092fef65d","order_by":2,"name":"James Jaworski","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"James","middleName":"","lastName":"Jaworski","suffix":""},{"id":310347148,"identity":"3147d58b-f639-4da7-9015-223d3f9b3923","order_by":3,"name":"Jinchuan Xing","email":"","orcid":"","institution":"Rutgers, The State University of New Jersey","correspondingAuthor":false,"prefix":"","firstName":"Jinchuan","middleName":"","lastName":"Xing","suffix":""},{"id":310347149,"identity":"bf53f9f0-5f56-4823-aaf6-e8b317c63465","order_by":4,"name":"Satoshi Okawa","email":"","orcid":"","institution":"University of Pittsburgh","correspondingAuthor":false,"prefix":"","firstName":"Satoshi","middleName":"","lastName":"Okawa","suffix":""},{"id":310347150,"identity":"77d7ea1e-60ee-4f42-8d4b-bb7945ecdace","order_by":5,"name":"Divay Chandra","email":"","orcid":"","institution":"University of Pittsburgh","correspondingAuthor":false,"prefix":"","firstName":"Divay","middleName":"","lastName":"Chandra","suffix":""},{"id":310347151,"identity":"375675c9-36b9-4e15-b9db-223ab1c9ab6a","order_by":6,"name":"Seyed Nouraie","email":"","orcid":"","institution":"University of Pittsburgh","correspondingAuthor":false,"prefix":"","firstName":"Seyed","middleName":"","lastName":"Nouraie","suffix":""},{"id":310347152,"identity":"6f09085d-919c-46bf-b5e1-f94f0af7f495","order_by":7,"name":"Toru Nyunoya","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYDADfijN2ECsDgnJBpK1GBwgVou5RI7Zg49tdnXGN3KPbvjBYCO74QABLZYzcswNZ7YlS5jdyEu72cOQZkxQi8GNHDNp3jZmoJYcs9sMDIcTidVSL2E8A6zlP9FaDksYSIC1HCBCy5lnZZIzzh2XnHHmHdAvBsnGMwlqOZ68TeJDWTU/f3vusRs/Kuxk+whpYRBIAMYFG4jFAzKBkHIQ4AcZ+gemZRSMglEwCkYBFgAAe55D/qOa5qEAAAAASUVORK5CYII=","orcid":"","institution":"VA Pittsburgh Healthcare System","correspondingAuthor":true,"prefix":"","firstName":"Toru","middleName":"","lastName":"Nyunoya","suffix":""}],"badges":[],"createdAt":"2024-05-24 22:53:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4474529/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4474529/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58153077,"identity":"46a46b56-2c39-415a-91e7-33ac31034d9d","added_by":"auto","created_at":"2024-06-11 20:25:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":657996,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of the identification of the single nucleotide polymorphisms (SNPs) associated with psoriasis and pulmonary function in the UK Biobank (UKBB) and the Vanderbilt University Medical Center Biobank (BioVU). Abbreviations: SNP=single nucleotide polymorphism, UKBB=the UK Biobank, BioVU= the Vanderbilt University Medical Center Biobank, FEV\u003csub\u003e1\u003c/sub\u003e=forced expiratory volume in one second, FVC=forced vital capacity.\u003c/p\u003e","description":"","filename":"PsoriasisandPulmFfigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4474529/v1/692e847bbcb9ec7fe1e96f88.png"},{"id":58155385,"identity":"db4d2e2f-f5e3-4de0-b9db-fb8b1be87113","added_by":"auto","created_at":"2024-06-11 20:49:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1405359,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4474529/v1/f6fe3343-c74f-47e6-a5aa-91d170851164.pdf"},{"id":58153767,"identity":"218ce737-408d-4b95-8764-c2ef89882506","added_by":"auto","created_at":"2024-06-11 20:33:40","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":58754,"visible":true,"origin":"","legend":"","description":"","filename":"PsoriasisandPFSupplTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4474529/v1/7beb93127590e4370c6cdc92.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Psoriasis and Pulmonary Function - Unveiling Genetic Connections","fulltext":[{"header":"Main Text","content":"\u003cp\u003ePsoriasis, an immune-mediated skin disease affecting 2% of the world\u0026rsquo;s population, characterized by well-demarcated, erythematous plaques with hyperkeratinization[1]. Beyond its cutaneous manifestations, psoriasis is often associated with chronic inflammatory diseases involving the cardiovascular, respiratory, and gastrointestinal systems. \u0026nbsp;Several genome-wide association studies (GWAS) identified genetic loci implicated in psoriasis that alter inflammatory pathways, including IL-23/IL-17, NFKB, and Type 1 interferon signaling, skin barrier integrity, and antigen presentation[2].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients with psoriasis exhibit a higher prevalence of pulmonary comorbidities, such as chronic obstructive pulmonary disease (COPD), asthma, and pneumonia, compared to individuals without psoriasis\u0026nbsp;[3-5]. The presence of psoriasis is linked to an increased rate of respiratory-related mortality\u0026nbsp;[6], suggesting that specific pulmonary manifestations in those with psoriasis may predict a poor prognosis. \u0026nbsp;Previous analyses have demonstrated an elevated risk of respiratory failure accompanied by asthma and airflow limitation, in psoriatic individuals[7]. Consequently, we propose that certain genetic variants linked to psoriasis may adversely affect lung function. This hypothesis was explored using data from two independent sources i.e., the UK Biobank (UKBB) and the\u0026nbsp;Vanderbilt University Medical Center Biobank (BioVU).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe UKBB is a large population-based database including biomedical, medical, and genetic information from approximately 500,000 participants\u0026nbsp;[8]. Genome-wide genotyping was performed using the UK Biobank Axiom Array. Approximately 850,000 markers were included, and the imputation was performed using IMPUTE4\u0026nbsp;[9]. Among the 63 previously reported psoriasis-associated single nucleotide polymorphisms (SNPs) from the European origin populations[10-14], we identified loci significantly associated with a self-reported diagnosis of psoriasis in White individuals controlling for age and sex using the UKBB database. If the originally reported psoriasis-associated SNPs were not available in the UKBB database, we analyzed their proxy SNPs with R2 \u0026gt;0.5 identified using LDproxy Tool (https://ldlink.nih.gov/?tab=ldproxy). We then determined whether the identified loci were significantly associated with pulmonary function (forced expiratory volume in one second [FEV\u003csub\u003e1\u003c/sub\u003e] in litter, forced vital capacity [FVC] in litter, and FEV\u003csub\u003e1\u003c/sub\u003e/FVC ratio). \u0026nbsp;To validate our findings, we used data from\u0026nbsp;BioVU[15]. BioVU participants were previously genotyped using the Illumina MEGA-Ex array and imputed with PLINK using the 1000 Genomes Project as a reference dataset. We identified White individuals participating in BioVU with available pulmonary function data and genome-wide genotyping data. Using the GENESIS software package[16], we conducted linear regression analyses, adjusting for age, age\u003csup\u003e2\u003c/sup\u003e, sex, smoking status (never/ever), and height. We used\u0026nbsp;Benjamini and Hochberg false discovery rate (FDR) method to highlight the genes that remain statistically significant after multiple comparisons in each cohort\u0026nbsp;[17]. FDR adjusted q-values were calculated and q\u0026lt;0.05 was considered significant.\u003c/p\u003e\n\u003cp\u003eOur analysis included 346,572 participants from the UKBB and 2,189 from BioVU. Of the 63 previously reported psoriasis-associated SNPs, 53 SNPs including 28 proxy SNPs were available for analysis in the UKBB. We confirmed that 31 of these 53 SNPs were significantly associated with a diagnosis of psoriasis in the UKBB participants (15 with higher risk and 16 with lower risk of psoriasis, Table E1). Among these 31 SNPs, 16 were significantly associated with FEV\u003csub\u003e1\u003c/sub\u003e, 14 were associated with FVC, and 5 were associated with FEV\u003csub\u003e1\u003c/sub\u003e/FVC (Table 1, 2, and Table E2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo validate these findings, we used data from\u0026nbsp;BioVU. Genotyping data on 27 of the\u0026nbsp;31 psoriasis-associated SNPs studied in the UKBB were available. The minor allele of rs8016947 (T)\u0026nbsp;was confirmed to be significant for a lower risk for psoriasis and higher FEV\u003csub\u003e1\u003c/sub\u003e (minor allele frequency (MAF) 0.435, beta 0.029, standard error (SE) 0.009, q=0.001 in the UKBB; MAF 0.435, beta 0.072, SE 0.021, q=0.001 in BioVU).\u0026nbsp;\u0026nbsp;The minor alleles of\u0026nbsp;rs17716942 (C) and rs8016947 (T)\u0026nbsp;were\u0026nbsp;significant for a lower risk for psoriasis and higher FVC\u0026nbsp;(For rs17716942, MAF 0.132, beta 0.174, SE 0.068, q=0.010 in the UKBB; MAF 0.145, beta 0.075, SE 0.034, q=0.025 in BioVU. For rs8016947, beta 0.040, SE 0.011, q\u0026lt;0.001 in the UKBB; beta 0.067, SE 0.024, q=0.005 in BioVU)\u0026nbsp;(Figure 1). Among 5 SNPs significantly associated with FEV\u003csub\u003e1\u003c/sub\u003e/FVC in the UKBB, none of these SNPs were statistically significant in BioVU.\u003c/p\u003e\n\u003cp\u003eThe present analysis revealed that the minor alleles of rs17716942 and rs8016947 were the unique SNPs significantly associated with a lower risk of psoriasis and higher FEV\u003csub\u003e1\u003c/sub\u003e and FVC in the two different cohort of UKBB and BioVU. The SNP rs17716942 is located in the\u0026nbsp;Potassium Voltage-Gated Channel Subfamily H Member 7 (\u003cem\u003eKCNH7\u003c/em\u003e) gene and multiple proxy SNPs with high linkage disequilibrium (LD) are located in the surrounding region. Genes such as the Interferon Induced With Helicase C Domain 1 gene (\u003cem\u003eIFIH1\u003c/em\u003e) and\u0026nbsp;Grancalcin gene (\u003cem\u003eGCA\u003c/em\u003e) are\u0026nbsp;located\u0026nbsp;in the associated region[18]. Polymorphisms in this \u003cem\u003eIFIH1\u003c/em\u003e-\u003cem\u003eGCA\u003c/em\u003e-\u003cem\u003eKCNH7\u003c/em\u003e locus are known to be associated with multiple sclerosis risk[19].\u0026nbsp;\u003cem\u003eKCNH7\u003c/em\u003e is primarily expressed in the brain tissue[20]\u0026nbsp;and its polymorphisms are reportedly associated with the treatment response of schizophrenia[21]. \u003cem\u003eIFIH1\u003c/em\u003e encodes the melanoma differentiation associated protein 5 (MDA5) which acts as a key intracellular sensor of viral RNA and triggers the innate immune response. The loss-of-function variants of the gene is reported to be associated with the development of very early onset Inflammatory bowel disease[22]. \u003cem\u003eGCA\u003c/em\u003e is a protein coding gene that encodes grancalcin. Grancalcin is mainly expressed in neutrophils and monocytes/macrophages and grancalcin deficient neutrophils are reported to be impaired in adhesion process[23]. Since \u003cem\u003eKCNH7\u003c/em\u003e is expressed at a low level in the lungs, the associated\u0026nbsp;\u003cem\u003eGCA\u003c/em\u003e and/or\u0026nbsp;\u003cem\u003eIFIH1\u003c/em\u003e may have a main role in the pathophysiology of psoriasis and impaired lung function. The SNP\u0026nbsp;rs8016947 is located near\u0026nbsp;(≃40kbp)\u0026nbsp;the NFKB Inhibitor Alpha gene (\u003cem\u003eNFKBIA\u003c/em\u003e).\u0026nbsp;NFKBIA is one of the most common regulatory proteins of NFKB, an important regulator of inflammatory responses. Polymorphisms of \u003cem\u003eNFKBIA\u003c/em\u003e are associated with various pulmonary diseases including atopic asthma, invasive pneumococcal disease, and trauma-associated acute lung injury[24-26]. Accordingly, there may be a potential genetic link between psoriasis and pulmonary comorbidities in altered inflammatory pathways, such as the innate virus response, the neutrophil adhesion, and the abnormal regulation of excessive inflammation. It is intriguing that \u003cem\u003eIFIH1\u003c/em\u003e, \u003cem\u003eGCA\u003c/em\u003e and \u003cem\u003eNFKBIA\u003c/em\u003e regulate innate immune response because\u0026nbsp;immunodysregulation responsible for the psoriasis pathogenesis may impair lung function as the systemic manifestation implicating a \u0026ldquo;skin-lung axis\u0026rdquo;.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere are some limitations in the present study. First, we evaluated only known SNPs associated with psoriasis in European ancestry populations because of limited availability of other racial/ethnic groups. Therefore, these identified SNPs linked to both psoriasis and pulmonary function in the present study may not be applicable for individuals of other ancestries. The narrowed analysis would limit its generalizability. Second, some potential confounding factors, such as the severity and medications (e.g., immunosuppressants) of psoriasis were not considered due to a lack of available data. Thus, the impact of the treatment or its adverse effect cannot be excluded. Finally, these finding could be impacted by the inflating type I error due to multiple comparisons in each study cohort.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, our findings shed light on several genetic variants that bridge psoriasis and lung function, paving the way for future research into the causal relationships underlying these associations in immune-mediated skin and lung diseases.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eK.T. contributed to the study design, analyzed the data, interpreted the data, and wrote the manuscript. M.C.A. contributed to the acquisition, analysis, and interpretation of the data and edited the manuscript.J.J., J.X., and S.O. contributed to the analysis and interpretation of the data.D.C. contributed to the data analysis and edited the manuscript. S.M.N. contributed to the study design, analyzed the data, interpreted the data, and edited the manuscript.T.N. designed the study, analyzed the data, interpreted the data, and edited the manuscript.T.N. takes responsibility for the integrity of the entire project, from its inception to the manuscript\u0026rsquo;s publication. All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChristophers E. Psoriasis\u0026ndash;epidemiology and clinical spectrum. Clin Exp Dermatol. 2001;26:314\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDand N, Mahil SK, Capon F, et al. Psoriasis and Genetics. Acta Derm Venereol. 2020;100:adv00030.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUngprasert P, Srivali N, Thongprayoon C. Association between psoriasis and chronic obstructive pulmonary disease: A systematic review and meta-analysis. J Dermatolog Treat. 2016;27:316\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFang HY, Liao WC, Lin CL, et al. Association between psoriasis and asthma: a population-based retrospective cohort analysis. Br J Dermatol. 2015;172:1066\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKao LT, Lee CZ, Liu SP, et al. Psoriasis and the risk of pneumonia: a population-based study. PLoS ONE. 2014;9:e116077.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eColaco K, Widdifield J, Luo J, et al. Trends in mortality and cause-specific mortality among patients with psoriasis and psoriatic arthritis in Ontario, Canada. J Am Acad Dermatol. 2021;84:1302\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanimura K, Nouraie SM, Chandra D, et al. Pulmonary comorbidities in psoriasis are associated with a high risk of respiratory failure. J Int Med Res. 2023;51:3000605231182881.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSudlow C, Gallacher J, Allen N, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12:e1001779.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBycroft C, Freeman C, Petkova D, et al. The UK Biobank resource with deep phenotyping and genomic data. Nature. 2018;562:203\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsoi LC, Stuart PE, Tian C, et al. Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants. Nat Commun. 2017;8:15382.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsoi LC, Spain SL, Knight J, et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet. 2012;44:1341\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsoi LC, Spain SL, Ellinghaus E, et al. Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci. Nat Commun. 2015;6:7001.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBowes J, Budu-Aggrey A, Huffmeier U, et al. Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis. Nat Commun. 2015;6:6046.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYin X, Low HQ, Wang L, et al. Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility. Nat Commun. 2015;6:6916.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoden DM, Pulley JM, Basford MA, et al. Development of a large-scale de-identified DNA biobank to enable personalized medicine. Clin Pharmacol Ther. 2008;84:362\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGogarten SM, Sofer T, Chen H, et al. Genetic association testing using the GENESIS R/Bioconductor package. Bioinformatics. 2019;35:5346\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenjamini Y, Yekutieli D. The control of the false discovery rate in multiple testing under dependency. Annals Stat. 2001;29:1165\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMachiela MJ, Chanock SJ. LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Bioinformatics. 2015;31:3555\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMart\u0026iacute;nez A, Santiago JL, C\u0026eacute;nit MC, et al. IFIH1-GCA-KCNH7 locus: influence on multiple sclerosis risk. Eur J Hum Genet. 2008;16:861\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFagerberg L, Hallstr\u0026ouml;m BM, Oksvold P, et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteom. 2014;13:397\u0026ndash;406.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang X, Su Y, Yan H, et al. Association Study of KCNH7 Polymorphisms and Individual Responses to Risperidone Treatment in Schizophrenia. Front Psychiatry. 2019;10:633.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCananzi M, Wohler E, Marzollo A, et al. IFIH1 loss-of-function variants contribute to very early-onset inflammatory bowel disease. Hum Genet. 2021;140:1299\u0026ndash;312.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu P, Roes J, Segal AW, et al. The role of grancalcin in adhesion of neutrophils. Cell Immunol. 2006;240:116\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark S-M, Chang H-S, Rhim T, et al. Association of IKBA gene polymorphisms with the development of asthma. Hum Immunol. 2010;71:1147\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSangil A, Arranz MJ, G\u0026uuml;erri-Fern\u0026aacute;ndez R, et al. Genetic susceptibility to invasive pneumococcal disease. Infect Genet Evol. 2018;59:126\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeyer NJ, Daye ZJ, Rushefski M, et al. SNP-set analysis replicates acute lung injury genetic risk factors. BMC Med Genet. 2012;13:52.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 The associations between psoriasis susceptibility loci and FEV\u003csub\u003e1\u0026nbsp;\u003c/sub\u003e(L) evaluated using an additive genetic model\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eSNP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eLocation\u003c/p\u003e\n \u003cp\u003e(GRCh38.p13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003eThe UKBB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\"\u003e\n \u003cp\u003eThe BioVU\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eProxy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ebeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eq value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eProxy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ebeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eq value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers4112788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr1:152578800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.341\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.042\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers41298997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr1:206481989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers17022427\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.237\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers4649203\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr1:24193430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.266\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.072\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.008\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.272\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers7536201\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr1:24966593\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers4265380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers4265380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.497\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers2201841\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr1:67228519\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.311\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.314\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.083\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers34517439\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr1:77984833\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers17391694\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers17716942\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr2:162404181\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.181\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.052\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.145\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers702873\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr2:60854407\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.429\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.049\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.451\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers10865331\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr2:62324337\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.379\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.389\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers20541\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr5:132660272\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers2082412\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr5:159290781\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.027\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n 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\u003cp\u003e\u003cstrong\u003e0.026\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.069\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers610604\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr6:137878280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.326\u003c/p\u003e\n \u003c/td\u003e\n 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valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.027\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.095\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n 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valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.369\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers11059675\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr12:122183779\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers7972875\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.481\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers2066808\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr12:56344189\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.068\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.085\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers9533962\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr13:44760058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers1415638\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.448\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers1415638\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.411\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.069\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers8016947\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr14:35363460\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.435\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.029\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.435\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.072\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers367569\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr16:11271643\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers243325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.304\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers243325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.291\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers10782001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr16:30931304\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.362\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers4795067\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr17:27779649\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.352\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.047\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.012\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.358\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers11652075\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr17:80205094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.499\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.072\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.498\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers545979\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr18:54293380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers602422\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers602422\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.297\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers12720356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr19:10359299\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.097\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers492602\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr19:48703160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.499\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.498\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers495337\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr20:49905793\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.424\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.042\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.417\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers181359\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr22:21574352\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.191\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.204\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable 2 The associations between psoriasis susceptibility loci and FVC\u003csub\u003e\u0026nbsp;\u003c/sub\u003e(L) evaluated using an additive genetic model\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eSNP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eLocation\u003c/p\u003e\n \u003cp\u003e(GRCh38.p13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003eUKBB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\"\u003e\n \u003cp\u003eBioVU\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eProxy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ebeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eq value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eProxy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ebeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eq value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers4112788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr1:152578800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.341\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers41298997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr1:206481989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers17022427\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.237\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers4649203\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr1:24193430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.266\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.088\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.272\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers7536201\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr1:24966593\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers4265380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers4265380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.497\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers2201841\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr1:67228519\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.311\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n 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\u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers2082412\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr5:159290781\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n 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\u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.031\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.371\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers33980500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr6:111592059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.075\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.046\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers610604\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr6:137878280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.326\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.077\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.330\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers12191877\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr6:31285148\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers61871342\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr10:100278884\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers17729876\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.413\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers2675662\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr10:73839369\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers2675671\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.451\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers2675671\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.423\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers1250544\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr10:79273128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.383\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.052\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.015\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.369\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers11059675\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr12:122183779\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers7972875\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.481\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers2066808\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr12:56344189\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.068\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.103\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers9533962\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr13:44760058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers1415638\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.448\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ers1415638\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.411\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e-0.056\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ers8016947\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003echr14:35363460\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.435\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.040\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n 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\u003c/table\u003e\n\u003c/div\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":"","lastPublishedDoi":"10.21203/rs.3.rs-4474529/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4474529/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePsoriasis, an immune-mediated skin disease characterized by erythematous plaques, is often associated with chronic lung diseases that impair pulmonary function. To investigate a potential genetic link between psoriasis and pulmonary function, we analyzed 63 previously reported psoriasis-associated single nucleotide polymorphisms (SNPs) for their associations with both psoriasis and pulmonary function measurements using data from the UK Biobank (UKBB) and Vanderbilt University Medical Center Biobank (BioVU). Our results confirm significant associations of specific SNPs with both the risk of psoriasis and changes in pulmonary function. Notably, the minor alleles of rs17716942 and rs8016947 were linked to a lower risk of psoriasis and improved pulmonary function across both biobank cohorts. These findings highlight potential genetic intersections involving immune regulation and inflammatory responses, mediated by genes such as IFIH1, GCA, and NFKBIA, which may underlie the observed \"skin-lung axis\" in psoriatic patients.\u003c/p\u003e","manuscriptTitle":"Psoriasis and Pulmonary Function - Unveiling Genetic Connections","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-11 20:25:35","doi":"10.21203/rs.3.rs-4474529/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":"a5fef9f8-2b4f-46c2-a7e6-d45045c44615","owner":[],"postedDate":"June 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-11T20:25:38+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-11 20:25:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4474529","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4474529","identity":"rs-4474529","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}