{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T19:15:19Z","timestamp":1770837319144,"version":"3.50.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"crossref","award":["No. 2022YFC2504003"],"award-info":[{"award-number":["No. 2022YFC2504003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Young Scholar Independent Innovation Science Fund of Chinese PLA General Hospital","award":["No. 22QNCZ020"],"award-info":[{"award-number":["No. 22QNCZ020"]}]},{"name":"Independent Research Fund of High-level Scientific and Technological Innovation Personnel Project","award":["[(2024)10]"],"award-info":[{"award-number":["[(2024)10]"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Observational studies highlighted a link between the appendix and inflammatory bowel disease (IBD), but proving causality has been difficult due to the lack of a clear temporal sequence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This research used a two-sample bidirectional univariable Mendelian randomization (MR), multivariable MR and linkage disequilibrium score regression (LDSC) analyses to explore the relationship between acute appendicitis, appendectomy, and IBD. Eligible instrumental variables were screened from previous genome-wide association studies (GWAS) of European ancestry for analysis. The inverse variance-weighted method was used for the primary analysis. Sensitivity analyses were used to detect and correct pleiotropy. LDSC analysis determined SNP-based heritability (h2) for acute appendicitis, IBD, Crohn\u2019s disease (CD), and ulcerative colitis (UC). Following that, cross-trait LDSC analysis assessed genetic correlations (rg) between these traits using GWAS summary data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genetically predicted UC was significantly associated with a lower risk of acute appendicitis (OR = 0.933, 95% CI 0.911\u20130.957, p\u2009&lt;\u20090.001) and appendectomy (OR = 0.954, 95% CI 0.932\u20130.976, p\u2009&lt;\u20090.001). Conversely, no causal effect was observed from acute appendicitis or appendectomy on IBD, UC, or CD. While a suggestive association was noted for CD with appendectomy in univariable analysis, it did not remain significant after multivariable adjustment for the influence of UC. A significant negative genetic correlation further supported the inverse relationship between UC and acute appendicitis (rg\u2009=\u2009\u22120.205, p\u2009=\u20090.005).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In conclusion, genetically predicted UC was causally associated with a decreased risk of acute appendicitis and appendectomy, but neither acute appendicitis nor appendectomy has a causal impact on the risk of IBD, UC, or CD. These findings suggest that ulcerative colitis (UC) may confer a protective effect against the development of acute appendicitis, offering valuable insights into the shared genetic architecture and potential biological mechanisms underlying these conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0342541","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:28:10Z","timestamp":1770834490000},"page":"e0342541","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evidence for genetic correlation between appendix and inflammatory bowel disease: A bidirectional Mendelian randomization 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An international cooperative study","volume":"22","author":"T Gilat","year":"1987","journal-title":"Scand J Gastroenterol"},{"issue":"2","key":"pone.0342541.ref035","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/ajg.2015.301","article-title":"The Link between the Appendix and Ulcerative Colitis: Clinical Relevance and Potential Immunological Mechanisms","volume":"111","author":"S Sahami","year":"2016","journal-title":"Am J Gastroenterol"},{"issue":"1","key":"pone.0342541.ref036","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1093\/ecco-jcc\/jjac111","article-title":"Risk Factors for Developing Inflammatory Bowel Disease Within and Across Families with a Family History of IBD","volume":"17","author":"J Torres","year":"2023","journal-title":"J Crohns Colitis"},{"key":"pone.0342541.ref037","doi-asserted-by":"crossref","first-page":"661752","DOI":"10.3389\/fmed.2021.661752","article-title":"Risk of Inflammatory Bowel Disease Following Appendectomy in Adulthood","volume":"8","author":"W-S Chung","year":"2021","journal-title":"Front Med (Lausanne)"},{"issue":"3","key":"pone.0342541.ref038","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.jcmgh.2022.10.016","article-title":"The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer","volume":"15","author":"MK Collard","year":"2023","journal-title":"Cell Mol Gastroenterol Hepatol"},{"issue":"3","key":"pone.0342541.ref039","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1136\/gut.2004.054353","article-title":"Environmental risk factors in paediatric inflammatory bowel diseases: a population based case control study","volume":"54","author":"S Baron","year":"2005","journal-title":"Gut"},{"issue":"5","key":"pone.0342541.ref040","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1097\/00042737-200205000-00010","article-title":"A case-control study of childhood environmental risk factors for the development of inflammatory bowel disease","volume":"14","author":"MA Feeney","year":"2002","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"4","key":"pone.0342541.ref041","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/apt.17392","article-title":"Antioxidants, minerals and vitamins in relation to Crohn\u2019s disease and ulcerative colitis: A Mendelian randomization study","volume":"57","author":"J Chen","year":"2023","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0342541.ref042","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12893-015-0017-1","article-title":"The ACCURE-trial: the effect of appendectomy on the clinical course of ulcerative colitis, a randomised international multicenter trial (NTR2883) and the ACCURE-UK trial: a randomised external pilot trial (ISRCTN56523019)","volume":"15","author":"TJ Gardenbroek","year":"2015","journal-title":"BMC Surg"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0342541","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:28:19Z","timestamp":1770834499000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0342541"}},"subtitle":[],"editor":[{"given":"Elham","family":"Kazemirad","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":42,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0342541","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]}}}