A Mendelian randomization study of daytime napping and inflammatory bowel disease

A Mendelian randomization study of daytime napping and inflammatory bowel disease | 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 Research Article A Mendelian randomization study of daytime napping and inflammatory bowel disease Sibo Li, Xu Gao, Yanbin Jiang, Lina Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8516533/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background Recently, the potential effects of daytime napping on inflammatory bowel disease has aroused great interest in research community. However, the causal relationship between daytime napping and inflammatory bowel disease remains uncertain. Methods A series of quality control steps were conducted to extract the eligible single nucleotide polymorphisms for the two-sample MR analysis. Next, we performed the Inverse Variance Weighted as the primary method to estimate causal effects, with the Weighted Median and Maximum Likelihood as the supplementary method. Furthermore, the Cochran's Q test, Egger intercept, MR-PRESSO and Leave-one-out method for sensitivity analyses. Results The initial MR analysis demonstrated that the daytime napping causally reduced the risk of inflammatory bowel disease ( OR = 0.327, P = 0.006) and ulcerative colitis ( OR = 0.300, P = 0.017), but the association was not found in the daytime napping and Crohn's disease ( OR = 0.520, P = 0.445). Additionally, consistent with the initial results, the replication analysis result showed that the daytime napping was a protective factor for UC ( OR = 0.988, P = 0.007), but no relation with inflammatory bowel disease ( OR = 1.006, P = 0.212). No significant evidence of heterogeneity and horizontal pleiotropy were identified by sensitivity analyses. Conclusion Our MR study supported the causal effect of daytime napping on ulcerative colitis, as well as into the prevention of ulcerative colitis pathogenesis through targeting sleep habit. Daytime napping Inflammatory bowel disease Ulcerative colitis Crohn's disease Mendelian randomization Figures Figure 1 Figure 2 Figure 3 Highlight Known: Daytime napping is a risk factor for or is not associated with IBD. New: Daytime napping was confirmed to have a protective effect on ulcerative colitis, but had no significant overall effect on Crohn's disease. Patient care: The study suggests that napping may be a new way to prevent ulcerative colitis, and further validation is needed to guide patients' daily habits. 1. Introducion Sleep is a key mediator of the human physiological health, and disruption of sleep homeostasis is closely contributed to the progression of several diseases[ 1 – 3 ]. Under most circumstances, sleep encompasses long-nighttime sleep and short naps. Numerous people routinely rejuvenate bodies and enhance mental vitality through short breaks or naps. However, short periods of sleep outside of the night, such as daytime napping, affecting the quality of the following sleep[ 4 ]. This feedback may promote the habit of daytime napping. Moreover, the daytime napping is considered as the potential risk factor of Alzheimer's Disease and some metabolic disease[ 5 – 6 ]. Research exploring the affect of napping on human health has garnered considerable attention and interest. Inflammatory bowel disease (IBD) is a chronic and nonspecific disease of gastrointestinal tract that might generate some serious complications. The Crohn's disease (CD) and ulcerative colitis (UC) are essential components of IBD, while those cases falling between the two classifications are referred to as IBD unclassified[ 7 ]. Patients with IBD have serious sleep disorders caused by malnutrition that due to intestinal underabsorption or increased catabolism[ 8 ]. Notably, the damaging of intestinal capillaries as a consequence of poor sleep quality can exacerbate this course[ 9 ]. This mechanism perpetuates a vicious feedback between sleep disorders and the IBD progression. Moreover, sleep disorders can also generate several psychiatric symptoms in IBD patients, such as anxiety and depression, which are closely related to the decline in patients' quality of life[ 10 ]. Therefore, improving the sleep quality in IBD patients may be a prospective adjuvant strategy. To date, the relationship between daytime napping and IBD remains controversial. A previous study found that sleep disorders, including daytime napping, did not support a causal relationship in the pathogenesis of IBD[ 11 ]. However, a recent prospective cohort study showed the positive association between daytime napping and IBD risk[ 12 ]. Therefore, the causal relationship between daytime napping and IBD are still questioned. Mendelian randomization (MR) analyses is a causal inference method based on genetic variants that utilize the effect of randomly assigned genotypes on phenotypes to infer the casual relationship between exposure and outcome[ 13 ]. In this study, we aimed to comprehensively illuminate the causal relationship between daytime napping and IBD by conducting two-sample Mendelian randomization analyses on summary statistics of UK Biobank[ 14 ] and FinnGen consortium[ 15 ]. 2. Methods 2.1 Study Design and Data Sources Our study design is depicted in Fig. 1 . In this work, we treated the daytime napping as the exposure, and the risk of IBD as the outcome. We sourced Genome Wide Association Study (GWAS) data on daytime napping and IBD from distinct databases to conduct initial MR analysis, effectively eliminating the potential population overlap. All details of these summary statistics showed in Table 1 . The FinnGen data of this study was obtained from the consortium's website ( https://www.finngen.fi/en ) after securing all necessary applications and permissions[ 15 ]. The UK Biobank data was provided by IEU OpenGWAS Project database ( https://gwas.mrcieu.ac.uk/ ), which is a publicly available resource that does not require specific permissions for the use of summary-level data[ 16 ]. 2.2 Selection of the Instrumental Variables The single nucleotide polymorphisms (SNPs) were selected as the instrumental variables (IVs) to investigate the causal relationship between daytime napping and IBD. We extracted SNPs that significantly associated with daytime napping ( P < 5×10 − 8 ) from ubk-b-4616 dataset ( Table 1 ) . Secondly, for avoiding the biased results caused by linkage disequilibrium (LD), the extracted SNPs were clumped with set LD r 2 < 0.001 and a window size of 10000 kb. Thirdly, according to the independence assumption, the genetic variants should not be associated with potential confounders. Therefore, we used the LDtrait tool to remove the potential confounding SNPs that associated with outcome, such as smoking, drink and schizophrenia[ 17 ]. Fourthly, SNPs with inconsistent alleles (i.e., A/G vs. A/C) and palindromic SNPs (i.e., A/T or G/C) were excluded. Eligible SNPs were extracted through these quality control procedures for subsequent MR analysis. According to the relevance assumption of MR analysis, selected SNPs should serve as the robust IVs for the exposure. To explore the presence of weak instrumental bias, F-statistics were used to evaluate the strength and validity of individual SNPs. F-statistics < 10 indicated weak instrumental bias in the IVs. 2.3 Statistic Analysis In this study, the Inverse Variance Weighted (IVW) test was performed as the primary method to estimate the causal relationship between daytime napping and IBD. Furthermore, the Weighted Median and Maximum Likelihood MR methods were used as supplementary analysis. The Weighted Median test reduces the affect of outliers or invalid IVs on the overall estimation, capturing potential causal relationships while maintaining the robustness of the analysis. The Maximum Likelihood was conducted to fine-tune the potential affect of sample overlap on causal estimation. Associations with P < 0.05 assessed by the above methods were considered signifcant. In order to further ensure the robustness of MR results, we conducted several sensitivity analyses. The Cochran's Q test was used to detect significant heterogeneity among the effects ( P > 0.05 was considered no significant heterogeneity). According to the exclusion restriction assumption, the genetic variants influence the outcome only through the exposure, not via other pathways. Therefore, we conducted Egger intercept test and MR-PRESSO global test to evaluate horizontal pleiotropy (P > 0.05 was considered no significant horizontal pleiotropy). Besides, Leave-one-out (LOO) analysis removes a specific SNP one at a time and then recalculates the MR analysis effect based on the remaining SNPs to assess the effect of a single SNP on the overall MR results. The R (version 4.4.1) package TwoSampleMR (version 0.6.4) and MR-PRESSO (version 1.0) were used to performed the statistical analyses[ 18 ]. 3. Results 3.1 Initial MR Analysis After careful screening, we obtained 22 eligible candidate SNPs for subsequent MR analysis. All SNPs F-statistics > 30, indicating no weak instrumental bias in the IVs (Supplementary Table S1 ) . The effect of daytime napping on IBD in the European population was assessed through MR analysis, with daytime napping as the exposure factor and IBD as the outcome. As shown in Fig. 2 A, the tests of IVW ( OR = 0.327, 95%CI = 0.147–0.703, P = 0.006), Weighted Median ( OR = 0.262, 95%CI = 0.085–0.803, P = 0.019) and Maximum Likelihood ( OR = 0.339, 95%CI = 0.150–0.766, P = 0.009) in initial analysis demonstrated that the daytime napping has potential causal relationship with IBD. Subsequently, we further investigated the casual effect of daytime napping on UC and CD. The result of initial MR analysis showed that daytime napping was the protective factor for UC (IVW model: OR = 0.300, 95%CI = 0.111–0.805, P = 0.017; Weighted Median model: OR = 0.267, 95%CI = 0.071–0.999, P = 0.049; Maximum Likelihood model: OR = 0.309, 95%CI = 0.114–0.839, P = 0.021) ( Fig. 2 B ) . However, no casual effect of daytime napping on CD was demonstrated in tests of IVW ( OR = 0.520, 95%CI = 0.097–2.783, P = 0.445), Weighted Median ( OR = 0.386, 95%CI = 0.036–4.132, P = 0.431) and Maximum Likelihood ( OR = 0.531, 95%CI = 0.097–2.903, P = 0.465) ( Fig. 2 B ) . 3.2 Replication MR analysis In addition, to ensure the robustness of the our initial MR results, we performed further replication analysis using UC and CD data from UK Biobank as the outcome factors. After a series of quality control steps, 18 SNPs associated with daytime napping and UC, 10 SNPs associated with daytime napping and CD, and all F -statistics > 30 (Supplementary Table S2 ) . Consistent with initial results, daytime napping was a protective factor for UC (IVW model: OR = 0.988, 95%CI = 0.980–0.997, P = 0.007; Maximum Likelihood model: OR = 0.988, 95%CI = 0.980–0.997, P = 0.008), while Weighted Median did not indicate statistical significance ( OR = 0.989, 95%CI = 0.977–1.001, P = 0.073) ( Fig. 2 C ) . Besides, when evaluating the casual effect of daytime napping on CD. None of the three tests indicated statistical significance (IVW model: OR = 1.006, 95%CI = 0.997–1.015, P = 0.212; Weighted Median model: OR = 1.010, 95%CI = 0.998–1.023, P = 0.116; Maximum Likelihood model: OR = 1.006, 95%CI = 0.997–1.015, P = 0.204) ( Fig. 2 C ) . 3.2 Sensitivity analysis The MR results underwent heterogeneity and horizontal pleiotropy analyses to further validate the causal relationship. As shown in Table 2 , the Cochran's Q test for IVW indicated no problems with heterogeneity ( P > 0.05). Furthermore, no significant evidence of horizontal pleiotropy was elucidated based on the Egger intercept ( P > 0.05) and MR-PRESSO (Global P > 0.05) tests ( Table 2 ). Finally, LOO analysis indicated that the MR results were not significantly affected by any single SNP ( Fig. 3 ) . 4. Discussion In this study, we used summary statistics from the FinnGen consortium and UK Biobank to systematically assess the potential causal effect of daytime napping on IBD and its two major subtypes, UC and CD, in a European population. The F -statistics of all SNPs > 30, ensuring the robustness of the IVs and excluding weak instrumental bias, allowing us to explore this complex relationship with statistical reliability. We applied rigorous methods, including IVW, Weighted Median, and Maximum Likelihood test to conduct MR analysis. The daytime napping was identified the protective factor for IBD and UC, but no relation with CD. Specifically, this result may be attributed to the ability of daytime napping to facilitate the restoration of intestinal immune function, mitigate inflammatory responses, and enhance gut microbiome balance[ 19 – 21 ]. Although the overlap of environmental factors in the development of IBD subtypes, the lifestyle habits or biorhythms may have different effects on UC and CD[ 22 , 23 ]. Moreover, there are notable distinctions in the location of lesions between the two diseases[ 24 ]. UC is mainly confined to the colon and rectum, and the lesions usually start from the rectum and extend to the proximal end, showing a continuous distribution. CD is a type of segmental and leaping inflammation that affects any part of the digestive tract, but most commonly occurs in the distal ileum and colon[ 25 – 27 ]. As a more complex and diverse disease, the onset of CD may be influenced by a combination of various genetic and environmental factors, making it difficult for single lifestyle changes to have a significant impact[ 28 ]. Therefore, more integrated and personalized strategies may be needed for the prevention and treatment of CD. Our study supported a causal effect of daytime napping on the pathogenesis of UC, but not on CD, contrary to a previous MR analysis[ 11 ]. This may be due to the risk of bias in the weak instrument of the selected IVs or failure to eliminate confounders in the earlier studies. Furthermore, a recent cohort study found a positive association between day-time napping and IBD[ 12 ]. Such contradictory findings could potentially stem from the inherent constraints of the cross-sectional study design. The effect of daytime napping on human health has become a topic of widespread interest, especially in relation to the development of chronic diseases[ 29 – 31 ]. As a nonspecific chronic inflammation, the pathogenesis of IBD is still unclear, but the morbidity is gradually increasing[ 32 ]. Generally, IBD is identified that caused by the interaction of multiple factors such as genetics and environment[ 33 ]. Therefore, exploring the relationship between daytime napping and IBD is a significant question. Notably, there are significant differences between UC and CD in clinical symptoms, metabolism, location of lesions and pathomorphology[ 23 , 26 , 27 ]. Therefore, UC and CD should not be roughly classified as IBD in the process of analysis. Furthermore, due to data limitations, we failed to analyze the causal relationship between napping and IBD unclassified. This work will be further discussed in the future. In conclusion, our findings provide valuable insights into the relationship between daytime napping and IBD and its major subtypes. However, the MR analysis relies on indirect evidence through genetic variation, additional research is necessary to validate these findings and explore the underlying biological mechanisms. Given the important role of lifestyle in the occurrence and development of chronic diseases, people should also be encouraged to pay attention to and improve their rest habits to promote intestinal health. Abbreviations IBD Inflammatory bowel disease UC Ulcerative colitis CD Crohn’s disease MR Mendelian randomization GWAS Genome-wide association study SNP Single nucleotide polymorphism IV Instrumental variable IVW Inverse variance weighted LOO Leave-one-out CI Confidence interval OR Odds ratio. Declarations Declarations Ethics approval and consent to participate All GWAS data were provided by UK Biobank and FinnGen consortium. This study did not require any public or patient.Therefore, no ethical approval was required. Consent for publication Not applicable. Competing Interests The authors declare that they have no competing interests. Funding This work was supported by the Heilongjiang Province Traditional Chinese Medicine Scientific Research Project (ZHY2025-158). The funder had no role in study design, data collection, analysis, interpretation, or manuscript writing. Author Contribution L.Z. conceived and designed the study, secured funding, and supervised the project. Y.J. performed the data curation, quality control, and statistical analysis, including the primary and supplementary Mendelian randomization estimates. X.G. conducted the sensitivity and replication analyses, and assisted with the interpretation of the results. S.L. drafted the initial manuscript and prepared the figures. All authors critically reviewed, edited, and approved the final version of the manuscript. Acknowledgement We thank the participants and researchers of the UK Biobank and FinnGen consortium for providing publicly available GWAS summary data. We are grateful for the assistance provided by Daqing Oilfield General Hospital and Harbin Medical University. Data Availability The GWAS summary statistics for daytime napping and inflammatory bowel disease (including ulcerative colitis and Crohn’s disease) are publicly available as follows:Daytime napping (ukb-b-4616): IEU OpenGWAS ProjectIBD, UC, and CD (FinnGen): FinnGen consortiumUC (ukb-b-7584) and CD (ukb-b-8210): IEU OpenGWAS ProjectThe R code used for the Mendelian randomization analyses is available from the corresponding author upon reasonable request. References Iranzo A, Cochen De, Cock V et al. Sleep and sleep disorders in people with Parkinson's disease. Hertenstein E, Benz F, Schneider CL, et al. Insomnia-A risk factor for mental disorders. J Sleep Res. 2023;32(6):e13930. Guo C, Harshfield EL, Markus HS. Sleep Characteristics and Risk of Stroke and Dementia: An Observational and Mendelian Randomization Study. Neurology. 2024;102(5):e209141. Franken P, Dijk DJ. 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Tables Table 1 Details of the GWAS data. Trait Source Dataset Ancestry Sample size Year Daytime napping UK Biobank ubk-b-4616 European 462,400 2018 IBD FinnGen K11_IBD_STRICT European 214,053 2021 UC FinnGen K11_UC_STRICT2 European 218,384 2021 UC UK Biobank ukb-b-7584 European 501,779 2018 CD FinnGen K11_CD_STRICT2 European 220,038 2021 CD UK Biobank ukb-b-8210 European 501,779 2018 Table.2 Heterogeneity and horizontal pleiotropy of MR analyzes Outcome Heterogeneity Pleiotropy Trait Source Inverse variance weighted Egger intercept PRESSO Q Q df P Se P Global P IBD FinnGen 16.938 21 0.715 0.018 0.419 0.735 UC FinnGen 11.769 21 0.946 0.022 0.707 0.95 CD FinnGen 19.384 21 0.561 0.037 0.290 0.559 UC UK Biobank 16.870 17 0.463 0.0002 0.065 0.458 CD UK Biobank 14.658 9 0.101 0.0003 0.264 0.114 Additional Declarations No competing interests reported. Supplementary Files SupplementaryTables.xlsx STROBEMRchecklistfillable.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 23 Feb, 2026 Reviews received at journal 18 Feb, 2026 Reviews received at journal 15 Feb, 2026 Reviewers agreed at journal 08 Feb, 2026 Reviewers agreed at journal 05 Feb, 2026 Reviewers agreed at journal 05 Feb, 2026 Reviewers invited by journal 05 Feb, 2026 Editor assigned by journal 03 Feb, 2026 Editor invited by journal 14 Jan, 2026 Submission checks completed at journal 13 Jan, 2026 First submitted to journal 13 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-8516533","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":587635079,"identity":"d25cd0e7-dbda-4dec-88f7-bfa029df01ad","order_by":0,"name":"Sibo Li","email":"","orcid":"","institution":"Daqing Oilfield General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sibo","middleName":"","lastName":"Li","suffix":""},{"id":587635080,"identity":"28a1020f-cd27-4eae-92d2-85567faf4585","order_by":1,"name":"Xu Gao","email":"","orcid":"","institution":"Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xu","middleName":"","lastName":"Gao","suffix":""},{"id":587635081,"identity":"558772ff-964b-466b-a8a9-ea621141dcce","order_by":2,"name":"Yanbin Jiang","email":"","orcid":"","institution":"Daqing Oilfield General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yanbin","middleName":"","lastName":"Jiang","suffix":""},{"id":587635082,"identity":"e7f7030d-7389-4c74-b5fb-90bea7a992fa","order_by":3,"name":"Lina Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYDACCRBRACTZmw8c+FBBtBYDIMlzLPHgjDPEawExcowP87YQoUN+dvOzh18MLPL4Z+R8OMDbwCDPL3YAvxbGOcfMjWUMJIolzrzdcEByB4PhzNkJ+LUwSySYSUsYSCQ2HM/dcMDwDEOCwW0CWtgk0r+Btcw/kPPgQGIbEVp4JHLMJD8AtWw4kcNw4CAxWiQkcsqkgYGcuPHMMYODDWckCPtFfkb6NskfFXWJ8443P/78p8JGnl+agBYQYOZBspWwchBg/EGculEwCkbBKBipAACfj0d8anzjJAAAAABJRU5ErkJggg==","orcid":"","institution":"Daqing Oilfield General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Lina","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2026-01-05 03:38:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8516533/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8516533/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102397528,"identity":"eafcca26-b7af-4644-b67c-6487d6ab0fc2","added_by":"auto","created_at":"2026-02-11 10:17:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":138930,"visible":true,"origin":"","legend":"\u003cp\u003eThe sturdy design of two-sample bidirectional Mendelian randomization analysis.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8516533/v1/fe711292adc821159b848d2c.png"},{"id":102343205,"identity":"27b1191b-3ab7-4d90-996f-7fbe098beacb","added_by":"auto","created_at":"2026-02-10 17:06:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":132597,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots for MR analyses of the causal effect of daytime napping on IBD, UC and CD. \u003cstrong\u003eA\u003c/strong\u003e. daytime napping-IBD (FinnGen). \u003cstrong\u003eB\u003c/strong\u003e. daytime napping-UC and CD (FinnGen). C. daytime napping-UC and CD (UK Biobank).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8516533/v1/b0ef349c58d06ffc8ff27841.png"},{"id":102343207,"identity":"71547895-3ee7-4f33-bb78-3b3e4ba9593c","added_by":"auto","created_at":"2026-02-10 17:06:53","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":933716,"visible":true,"origin":"","legend":"\u003cp\u003eLeave-one-out analysis for all MR results.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8516533/v1/94636ab379e9acd1693325fa.jpeg"},{"id":102399049,"identity":"7a919397-d0e8-46be-86e0-812b31dc74db","added_by":"auto","created_at":"2026-02-11 10:32:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1828050,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8516533/v1/969d223c-9a36-45f8-ba30-430768192c70.pdf"},{"id":102343203,"identity":"c3d9ae3b-e943-4ec3-aafd-c5ead6793c9e","added_by":"auto","created_at":"2026-02-10 17:06:53","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":14704,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTables.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8516533/v1/5d2ba81a990bc65146c6e17c.xlsx"},{"id":102343206,"identity":"875b5e22-d4f7-4c1a-81ae-4ca67e6cf05c","added_by":"auto","created_at":"2026-02-10 17:06:53","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":130381,"visible":true,"origin":"","legend":"","description":"","filename":"STROBEMRchecklistfillable.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8516533/v1/b90feef4a25cd096de50a56b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Mendelian randomization study of daytime napping and inflammatory bowel disease","fulltext":[{"header":"Highlight","content":"\u003cp\u003e\u003cstrong\u003eKnown:\u003c/strong\u003e Daytime napping is a risk factor for or is not associated with IBD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNew:\u003c/strong\u003e Daytime napping was confirmed to have a protective effect on ulcerative colitis, but had no significant overall effect on Crohn's disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient care:\u003c/strong\u003e The study suggests that napping may be a new way to prevent ulcerative colitis, and further validation is needed to guide patients' daily habits.\u003c/p\u003e"},{"header":"1. Introducion","content":"\u003cp\u003eSleep is a key mediator of the human physiological health, and disruption of sleep homeostasis is closely contributed to the progression of several diseases[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Under most circumstances, sleep encompasses long-nighttime sleep and short naps. Numerous people routinely rejuvenate bodies and enhance mental vitality through short breaks or naps. However, short periods of sleep outside of the night, such as daytime napping, affecting the quality of the following sleep[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. This feedback may promote the habit of daytime napping. Moreover, the daytime napping is considered as the potential risk factor of Alzheimer's Disease and some metabolic disease[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Research exploring the affect of napping on human health has garnered considerable attention and interest.\u003c/p\u003e \u003cp\u003eInflammatory bowel disease (IBD) is a chronic and nonspecific disease of gastrointestinal tract that might generate some serious complications. The Crohn's disease (CD) and ulcerative colitis (UC) are essential components of IBD, while those cases falling between the two classifications are referred to as IBD unclassified[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Patients with IBD have serious sleep disorders caused by malnutrition that due to intestinal underabsorption or increased catabolism[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Notably, the damaging of intestinal capillaries as a consequence of poor sleep quality can exacerbate this course[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This mechanism perpetuates a vicious feedback between sleep disorders and the IBD progression. Moreover, sleep disorders can also generate several psychiatric symptoms in IBD patients, such as anxiety and depression, which are closely related to the decline in patients' quality of life[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore, improving the sleep quality in IBD patients may be a prospective adjuvant strategy.\u003c/p\u003e \u003cp\u003eTo date, the relationship between daytime napping and IBD remains controversial. A previous study found that sleep disorders, including daytime napping, did not support a causal relationship in the pathogenesis of IBD[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, a recent prospective cohort study showed the positive association between daytime napping and IBD risk[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Therefore, the causal relationship between daytime napping and IBD are still questioned.\u003c/p\u003e \u003cp\u003eMendelian randomization (MR) analyses is a causal inference method based on genetic variants that utilize the effect of randomly assigned genotypes on phenotypes to infer the casual relationship between exposure and outcome[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In this study, we aimed to comprehensively illuminate the causal relationship between daytime napping and IBD by conducting two-sample Mendelian randomization analyses on summary statistics of UK Biobank[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and FinnGen consortium[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Design and Data Sources\u003c/h2\u003e \u003cp\u003eOur study design is depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In this work, we treated the daytime napping as the exposure, and the risk of IBD as the outcome. We sourced Genome Wide Association Study (GWAS) data on daytime napping and IBD from distinct databases to conduct initial MR analysis, effectively eliminating the potential population overlap. All details of these summary statistics showed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The FinnGen data of this study was obtained from the consortium's website (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.finngen.fi/en\u003c/span\u003e\u003cspan address=\"https://www.finngen.fi/en\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) after securing all necessary applications and permissions[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The UK Biobank data was provided by IEU OpenGWAS Project database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://gwas.mrcieu.ac.uk/\u003c/span\u003e\u003cspan address=\"https://gwas.mrcieu.ac.uk/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), which is a publicly available resource that does not require specific permissions for the use of summary-level data[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Selection of the Instrumental Variables\u003c/h2\u003e \u003cp\u003eThe single nucleotide polymorphisms (SNPs) were selected as the instrumental variables (IVs) to investigate the causal relationship between daytime napping and IBD. We extracted SNPs that significantly associated with daytime napping (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;5\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;8\u003c/sup\u003e) from ubk-b-4616 dataset \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Secondly, for avoiding the biased results caused by linkage disequilibrium (LD), the extracted SNPs were clumped with set LD \u003cem\u003er\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 and a window size of 10000 kb. Thirdly, according to the independence assumption, the genetic variants should not be associated with potential confounders. Therefore, we used the LDtrait tool to remove the potential confounding SNPs that associated with outcome, such as smoking, drink and schizophrenia[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Fourthly, SNPs with inconsistent alleles (i.e., A/G vs. A/C) and palindromic SNPs (i.e., A/T or G/C) were excluded. Eligible SNPs were extracted through these quality control procedures for subsequent MR analysis.\u003c/p\u003e \u003cp\u003eAccording to the relevance assumption of MR analysis, selected SNPs should serve as the robust IVs for the exposure. To explore the presence of weak instrumental bias, F-statistics were used to evaluate the strength and validity of individual SNPs. F-statistics\u0026thinsp;\u0026lt;\u0026thinsp;10 indicated weak instrumental bias in the IVs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Statistic Analysis\u003c/h2\u003e \u003cp\u003eIn this study, the Inverse Variance Weighted (IVW) test was performed as the primary method to estimate the causal relationship between daytime napping and IBD. Furthermore, the Weighted Median and Maximum Likelihood MR methods were used as supplementary analysis. The Weighted Median test reduces the affect of outliers or invalid IVs on the overall estimation, capturing potential causal relationships while maintaining the robustness of the analysis. The Maximum Likelihood was conducted to fine-tune the potential affect of sample overlap on causal estimation. Associations with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 assessed by the above methods were considered signifcant.\u003c/p\u003e \u003cp\u003eIn order to further ensure the robustness of MR results, we conducted several sensitivity analyses. The Cochran's Q test was used to detect significant heterogeneity among the effects (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05 was considered no significant heterogeneity). According to the exclusion restriction assumption, the genetic variants influence the outcome only through the exposure, not via other pathways. Therefore, we conducted Egger intercept test and MR-PRESSO global test to evaluate horizontal pleiotropy (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05 was considered no significant horizontal pleiotropy). Besides, Leave-one-out (LOO) analysis removes a specific SNP one at a time and then recalculates the MR analysis effect based on the remaining SNPs to assess the effect of a single SNP on the overall MR results. The R (version 4.4.1) package TwoSampleMR (version 0.6.4) and MR-PRESSO (version 1.0) were used to performed the statistical analyses[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Initial MR Analysis\u003c/h2\u003e \u003cp\u003eAfter careful screening, we obtained 22 eligible candidate SNPs for subsequent MR analysis. All SNPs F-statistics\u0026thinsp;\u0026gt;\u0026thinsp;30, indicating no weak instrumental bias in the IVs \u003cb\u003e(Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eThe effect of daytime napping on IBD in the European population was assessed through MR analysis, with daytime napping as the exposure factor and IBD as the outcome. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA, the tests of IVW (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.327, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.147\u0026ndash;0.703, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006), Weighted Median ( \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.262, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.085\u0026ndash;0.803, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.019) and Maximum Likelihood (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.339, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.150\u0026ndash;0.766, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009) in initial analysis demonstrated that the daytime napping has potential causal relationship with IBD. Subsequently, we further investigated the casual effect of daytime napping on UC and CD. The result of initial MR analysis showed that daytime napping was the protective factor for UC (IVW model: \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.300, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.111\u0026ndash;0.805, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017; Weighted Median model: \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.267, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.071\u0026ndash;0.999, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049; Maximum Likelihood model: \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.309, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.114\u0026ndash;0.839, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB\u003cb\u003e)\u003c/b\u003e. However, no casual effect of daytime napping on CD was demonstrated in tests of IVW (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.520, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.097\u0026ndash;2.783, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.445), Weighted Median (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.386, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.036\u0026ndash;4.132, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.431) and Maximum Likelihood (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.531, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.097\u0026ndash;2.903, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.465) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Replication MR analysis\u003c/h2\u003e \u003cp\u003eIn addition, to ensure the robustness of the our initial MR results, we performed further replication analysis using UC and CD data from UK Biobank as the outcome factors. After a series of quality control steps, 18 SNPs associated with daytime napping and UC, 10 SNPs associated with daytime napping and CD, and all \u003cem\u003eF\u003c/em\u003e-statistics\u0026thinsp;\u0026gt;\u0026thinsp;30 \u003cb\u003e(Supplementary Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eConsistent with initial results, daytime napping was a protective factor for UC (IVW model: \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.988, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.980\u0026ndash;0.997, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007; Maximum Likelihood model: \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.988, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.980\u0026ndash;0.997, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008), while Weighted Median did not indicate statistical significance (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.989, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.977\u0026ndash;1.001, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.073) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC\u003cb\u003e)\u003c/b\u003e. Besides, when evaluating the casual effect of daytime napping on CD. None of the three tests indicated statistical significance (IVW model: \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.006, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.997\u0026ndash;1.015, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.212; Weighted Median model: \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.010, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.998\u0026ndash;1.023, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.116; Maximum Likelihood model: \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.006, \u003cem\u003e95%CI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.997\u0026ndash;1.015, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.204) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Sensitivity analysis\u003c/h2\u003e \u003cp\u003eThe MR results underwent heterogeneity and horizontal pleiotropy analyses to further validate the causal relationship. As shown in \u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e, the Cochran's Q test for IVW indicated no problems with heterogeneity (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Furthermore, no significant evidence of horizontal pleiotropy was elucidated based on the Egger intercept (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) and MR-PRESSO (Global \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) tests (\u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e). Finally, LOO analysis indicated that the MR results were not significantly affected by any single SNP \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this study, we used summary statistics from the FinnGen consortium and UK Biobank to systematically assess the potential causal effect of daytime napping on IBD and its two major subtypes, UC and CD, in a European population. The \u003cem\u003eF\u003c/em\u003e-statistics of all SNPs\u0026thinsp;\u0026gt;\u0026thinsp;30, ensuring the robustness of the IVs and excluding weak instrumental bias, allowing us to explore this complex relationship with statistical reliability. We applied rigorous methods, including IVW, Weighted Median, and Maximum Likelihood test to conduct MR analysis. The daytime napping was identified the protective factor for IBD and UC, but no relation with CD.\u003c/p\u003e \u003cp\u003eSpecifically, this result may be attributed to the ability of daytime napping to facilitate the restoration of intestinal immune function, mitigate inflammatory responses, and enhance gut microbiome balance[\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Although the overlap of environmental factors in the development of IBD subtypes, the lifestyle habits or biorhythms may have different effects on UC and CD[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Moreover, there are notable distinctions in the location of lesions between the two diseases[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. UC is mainly confined to the colon and rectum, and the lesions usually start from the rectum and extend to the proximal end, showing a continuous distribution. CD is a type of segmental and leaping inflammation that affects any part of the digestive tract, but most commonly occurs in the distal ileum and colon[\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. As a more complex and diverse disease, the onset of CD may be influenced by a combination of various genetic and environmental factors, making it difficult for single lifestyle changes to have a significant impact[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Therefore, more integrated and personalized strategies may be needed for the prevention and treatment of CD.\u003c/p\u003e \u003cp\u003eOur study supported a causal effect of daytime napping on the pathogenesis of UC, but not on CD, contrary to a previous MR analysis[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This may be due to the risk of bias in the weak instrument of the selected IVs or failure to eliminate confounders in the earlier studies. Furthermore, a recent cohort study found a positive association between day-time napping and IBD[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Such contradictory findings could potentially stem from the inherent constraints of the cross-sectional study design.\u003c/p\u003e \u003cp\u003eThe effect of daytime napping on human health has become a topic of widespread interest, especially in relation to the development of chronic diseases[\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. As a nonspecific chronic inflammation, the pathogenesis of IBD is still unclear, but the morbidity is gradually increasing[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Generally, IBD is identified that caused by the interaction of multiple factors such as genetics and environment[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Therefore, exploring the relationship between daytime napping and IBD is a significant question. Notably, there are significant differences between UC and CD in clinical symptoms, metabolism, location of lesions and pathomorphology[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Therefore, UC and CD should not be roughly classified as IBD in the process of analysis. Furthermore, due to data limitations, we failed to analyze the causal relationship between napping and IBD unclassified. This work will be further discussed in the future.\u003c/p\u003e \u003cp\u003eIn conclusion, our findings provide valuable insights into the relationship between daytime napping and IBD and its major subtypes. However, the MR analysis relies on indirect evidence through genetic variation, additional research is necessary to validate these findings and explore the underlying biological mechanisms. Given the important role of lifestyle in the occurrence and development of chronic diseases, people should also be encouraged to pay attention to and improve their rest habits to promote intestinal health.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIBD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInflammatory bowel disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUlcerative colitis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCrohn\u0026rsquo;s disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMendelian randomization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGWAS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGenome-wide association study\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSNP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSingle nucleotide polymorphism\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInstrumental variable\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIVW\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInverse variance weighted\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLOO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLeave-one-out\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eConfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOdds ratio.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eDeclarations\u003c/h2\u003e\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003eAll GWAS data were provided by UK Biobank and FinnGen consortium. This study did not require any public or patient.Therefore, no ethical approval was required.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work was supported by the Heilongjiang Province Traditional Chinese Medicine Scientific Research Project (ZHY2025-158). The funder had no role in study design, data collection, analysis, interpretation, or manuscript writing.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eL.Z. conceived and designed the study, secured funding, and supervised the project. Y.J. performed the data curation, quality control, and statistical analysis, including the primary and supplementary Mendelian randomization estimates. X.G. conducted the sensitivity and replication analyses, and assisted with the interpretation of the results. S.L. drafted the initial manuscript and prepared the figures. All authors critically reviewed, edited, and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank the participants and researchers of the UK Biobank and FinnGen consortium for providing publicly available GWAS summary data. We are grateful for the assistance provided by Daqing Oilfield General Hospital and Harbin Medical University.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe GWAS summary statistics for daytime napping and inflammatory bowel disease (including ulcerative colitis and Crohn\u0026rsquo;s disease) are publicly available as follows:Daytime napping (ukb-b-4616): IEU OpenGWAS ProjectIBD, UC, and CD (FinnGen): FinnGen consortiumUC (ukb-b-7584) and CD (ukb-b-8210): IEU OpenGWAS ProjectThe R code used for the Mendelian randomization analyses is available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eIranzo A, Cochen De, Cock V et al. Sleep\u0026ensp;and\u0026ensp;sleep\u0026ensp;disorders in people with Parkinson's\u0026ensp;disease.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHertenstein E, Benz F, Schneider CL, et al. Insomnia-A risk factor for mental disorders. J Sleep Res. 2023;32(6):e13930.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuo C, Harshfield EL, Markus HS. Sleep Characteristics and Risk of Stroke and Dementia: An Observational and Mendelian Randomization Study. Neurology. 2024;102(5):e209141.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFranken P, Dijk DJ. Sleep and circadian rhythmicity as entangled processes serving homeostasis. Nat Rev Neurosci. 2024; (1):43\u0026ndash;59.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRan S, Lin X, Liu B. A Mendelian randomization study of Alzheimer's disease and daytime napping. Alzheimers Dement. 2024;20(1):741\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang J, Wu Z, Jin X, et al. Bidirectional Associations between Daytime Napping Duration and Metabolic Syndrome: A Nationally Representative Cohort Study. 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PLoS Med. 2015;12(3):e1001779.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKurki MI, Karjalainen J, Palta P, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;613(7944):508\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatthew Lyon, Shea J, Andrews B, Elsworth, et al. The variant call format provides efficient and robust storage of GWAS summary statistics. Genome Biol. 2021;22(1):32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin SH, Thakur R, Machiela MJ. LDexpress: an online tool for integrating population-specific linkage disequilibrium patterns with tissue-specific expression data. BMC Bioinformatics. 2021;22(1):608.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHemani G, Zheng J, Elsworth B, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFaraut B, Boudjeltia KZ, Dyzma M, et al. Benefits of napping and an extended duration of recovery sleep on alertness and immune cells after acute sleep restriction. Brain Behav Immun. 2011;25(1):16\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFaraut B, Boudjeltia KZ, Vanhamme L, et al. Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery. Sleep Med Rev. 2012;16(2):137\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolzhausen EA, Peppard PE, Sethi AK, et al. Associations of gut microbiome richness and diversity with objective and subjective sleep measures in a population sample. Sleep. 2024;47(3):zsad300.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnanthakrishnan AN, Khalili H, Konijeti GG, et al. A prospective study of long-term intake of dietary fiber and risk of Crohn's disease and ulcerative colitis. Gastroenterology. 2013;145(5):970\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdolph TE, Meyer M, Schw\u0026auml;rzler J, et al. The metabolic nature of inflammatory bowel diseases. Nat Rev Gastroenterol Hepatol. 2022;19(12):753\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBattistini C, Ballan R, Herkenhoff ME, et al. Vitamin D Modulates Intestinal Microbiota in Inflammatory Bowel Diseases. Int J Mol Sci. 2020;22(1):362.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAGA Patient Information Section. Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2017;15:A21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUngaro R, Mehandru S, Allen PB, et al. Ulcerative colitis. Lancet. 2017;389(10080):1756\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTorres J, Mehandru S, Colombel JF, et al. Crohn's disease. Lancet. 2017;389(10080):1741\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKong L, Pokatayev V, Lefkovith A, et al. The landscape of immune dysregulation in Crohn's disease revealed through single-cell transcriptomic profiling in the ileum and colon. Immunity. 2023;56(2):444\u0026ndash;e4585.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang YB, Zheng YB, Sun J, et al. Evidence from a meta-analysis of cohort studies of habitual daytime napping and health outcomes. Sleep Med Rev. 2024;78:101989.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWannamethee SG. Napping and Obesity in Adults - What do we Know? Curr Diab Rep; 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun J, Ma C, Zhao M, et al. Daytime napping and cardiovascular risk factors, cardiovascular disease, and mortality: A systematic review. Sleep Med Rev. 2022;65:101682.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang R, Li Z, Liu S, et al. Global, regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019: a systematic analysis based on the Global Burden of Disease Study 2019. BMJ Open. 2023;13(3):e065186.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgrawal M, Allin KH, Petralia F, et al. Multiomics to elucidate inflammatory bowel disease risk factors and pathways. Nat Rev Gastroenterol Hepatol. 2022;19(6):399\u0026ndash;409.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDetails of the GWAS data.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTrait\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSource\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDataset\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAncestry\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSample size\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYear\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDaytime napping\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUK Biobank\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eubk-b-4616\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEuropean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e462,400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFinnGen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eK11_IBD_STRICT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEuropean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e214,053\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFinnGen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eK11_UC_STRICT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEuropean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e218,384\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUK Biobank\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eukb-b-7584\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEuropean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e501,779\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFinnGen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eK11_CD_STRICT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEuropean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e220,038\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUK Biobank\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eukb-b-8210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEuropean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e501,779\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;Table.2 Heterogeneity and horizontal pleiotropy of MR analyzes\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Taba\" border=\"1\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eOutcome\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eHeterogeneity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003ePleiotropy\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eTrait\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eSource\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eInverse variance weighted\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eEgger intercept\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003ePRESSO\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eQ\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eQ df\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eSe\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\"\u003eGlobal\u003c/span\u003e \u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eIBD\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFinnGen\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e16.938\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e21\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.715\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.018\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.419\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.735\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUC\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFinnGen\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e11.769\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e21\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.946\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.022\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.707\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.95\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eCD\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFinnGen\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e19.384\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e21\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.561\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.037\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.290\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.559\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUC\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUK Biobank\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e16.870\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e17\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.463\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.0002\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.065\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.458\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eCD\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUK Biobank\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e14.658\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e9\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.101\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.0003\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.264\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.114\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Daytime napping, Inflammatory bowel disease, Ulcerative colitis, Crohn's disease, Mendelian randomization","lastPublishedDoi":"10.21203/rs.3.rs-8516533/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8516533/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eRecently, the potential effects of daytime napping on inflammatory bowel disease has aroused great interest in research community. However, the causal relationship between daytime napping and inflammatory bowel disease remains uncertain.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA series of quality control steps were conducted to extract the eligible single nucleotide polymorphisms for the two-sample MR analysis. Next, we performed the Inverse Variance Weighted as the primary method to estimate causal effects, with the Weighted Median and Maximum Likelihood as the supplementary method. Furthermore, the Cochran's Q test, Egger intercept, MR-PRESSO and Leave-one-out method for sensitivity analyses.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe initial MR analysis demonstrated that the daytime napping causally reduced the risk of inflammatory bowel disease (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.327, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006) and ulcerative colitis (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.300, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017), but the association was not found in the daytime napping and Crohn's disease (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.520, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.445). Additionally, consistent with the initial results, the replication analysis result showed that the daytime napping was a protective factor for UC (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.988, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007), but no relation with inflammatory bowel disease (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.006, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.212). No significant evidence of heterogeneity and horizontal pleiotropy were identified by sensitivity analyses.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur MR study supported the causal effect of daytime napping on ulcerative colitis, as well as into the prevention of ulcerative colitis pathogenesis through targeting sleep habit.\u003c/p\u003e","manuscriptTitle":"A Mendelian randomization study of daytime napping and inflammatory bowel disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-10 17:06:46","doi":"10.21203/rs.3.rs-8516533/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-23T07:41:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-18T12:26:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-15T07:28:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"12855143900396414027049962665690641120","date":"2026-02-08T07:13:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"237767413340053369288219315326186382002","date":"2026-02-06T03:40:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"296143763351600578117151053752328742793","date":"2026-02-05T20:11:59+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-05T20:10:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-03T06:26:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-14T12:51:24+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-13T05:32:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2026-01-13T05:24:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ec7230fb-b554-4c49-9e30-7919cb34afca","owner":[],"postedDate":"February 10th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-10T17:06:46+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-10 17:06:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8516533","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8516533","identity":"rs-8516533","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}