{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:36:28Z","timestamp":1792254988351,"version":"4.4.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>An association between primary biliary cholangitis (PBC) and connective tissue diseases (CTDs) [rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sj\u00f6gren\u2019s syndrome (SS), systemic sclerosis (SSc)] has been found in observational studies. However, the direction causality is unclear. The aim of this study was to assess the causality between PBC and CTDs and to promote early screening, pre-emptive therapy, and accurate stratification.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between PBC [Genome-Wide Association Study (GWAS) meta-analysis, 8021 cases\/16498 controls], and SLE (GWAS meta-analysis, 8021 cases\/16489 controls), RA(FinnGen, 6236 cases\/14727 controls), SS(FinnGen, 2495 cases\/365533 controls), SSc (FinnGen, 302 cases\/213145 controls). Inverse variance weighting (IVW) was used as the primary analysis method, supplemented by four sensitivity analyses to assess the robustness of the results.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The IVW revealed that genetically predicted PBC increased the risk of SLE [odd\u2019s ratio (OR) = 1.43, 95% confidence interval (CI) 1.30\u20131.58, P &lt; 0.001]), RA (OR = 1.09, 95%CI1.04\u20131.14, P&lt;0.001), and SS (OR = 1.18, 95%CI1.12\u20131.24, P&lt;0.001), but not that of SSc. In addition, no association was observed between CTDs as an exposure and PBC. Sensitivity analyses did not reveal horizontal pleiotropy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our study provided new genetic evidence for a causal relationship between PBC and CTDs. PBC increased the risk of SLE, RA, and SS. Our findings highlighted the importance of active screening and intervention for CTDs in patients with PBC.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0298225","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T18:26:54Z","timestamp":1707503214000},"page":"e0298225","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Genetic link between primary biliary cholangitis and connective tissue diseases in European populations: A two-sample Mendelian randomization study"],"prefix":"10.1371","volume":"19","author":[{"given":"Zhekang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0432-3638","authenticated-orcid":true,"given":"Xinwang","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,2,9]]},"reference":[{"key":"pone.0298225.ref001","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jhep.2017.03.022","article-title":"EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis","volume":"67","author":"European Association for the Study of the Liver","year":"2017","journal-title":"J Hepatol"},{"key":"pone.0298225.ref002","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41575-019-0226-7","article-title":"Primary biliary cholangitis: pathogenesis and therapeutic opportunities","volume":"17","author":"AF Gulamhusein","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"pone.0298225.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3350\/cmh.2020.0028","article-title":"Current understanding of primary biliary cholangitis","volume":"27","author":"A. 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