{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:42:33Z","timestamp":1772995353933,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T00:00:00Z","timestamp":1752969600000},"content-version":"vor","delay-in-days":200,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070631"],"award-info":[{"award-number":["82070631"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Canadian Journal of Gastroenterology and Hepatology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that is commonly associated with various other autoimmune disorders. We conducted a phenome\u2010wide association study Mendelian randomization (MR\u2010PheWAS) to determine genetic association between PBC and other diseases, particularly autoimmune disorders.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    We performed a PheWAS to investigate the causal associations between PBC and related traits by conducting enrichment analysis of 35 PBC risk loci identified by prior GWAS and their matched control SNP sets in UK Biobank database. MR\u2010PheWAS and bidirectional two\u2010sample Mendelian randomization analysis were conducted to determine causal association between PBC and hypothyroidism. Colocalization analysis was conducted to investigate common genetic variants with hypothyroidism.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Genetic liability to PBC was associated with a higher risk of 25 traits (hypothyroidism, asthma, allergic rhinitis, psoriasis, ulcerative colitis, and multiple sclerosis). After false discovery rate (FDR) correction, there exist 9 traits significantly difference. MR\u2010PheWAS analysis demonstrated causal association between PBC and hypothyroidism, and bidirectional two\u2010sample Mendelian randomization analysis was performed to validate it. The OR of hypothyroidism on PBC was 113.61(\n                    <jats:italic>p<\/jats:italic>\n                    = 9.30E \u2212 05), and PBC was also causally associated with hypothyroidism (OR: 1.005;\n                    <jats:italic>p<\/jats:italic>\n                    = 4.33E \u2212 09). Among the genes identified, CCDC88B and MMEL1 were found to have positive associations with the risk of hypothyroidism (CCDC88B: OR\u2009=\u20091.004,\n                    <jats:italic>p<\/jats:italic>\n                    = 4.69E \u2212 07; MMEL1: OR\u2009=\u20091.004,\n                    <jats:italic>p<\/jats:italic>\n                    = 6.65E \u2212 06) and FinnGen cohorts (CCDC88B: OR\u2009=\u20091.044; MMEL1: OR\u2009=\u20091.038). The two genes may be the drug targets for hypothyroidism (CCDC88B: coloc.abf\u2010PPH4\u2009=\u200994.7%; MMEL1: coloc.abf\u2010PPH4\u2009=\u200991.8%).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    Our study revealed genetic association between PBC and hypothyroidism through a phenome\u2010wide Mendelian randomization, and then, colocalization identified two potential drug targets for hypothyroidism.\n                  <\/jats:p>","DOI":"10.1155\/cjgh\/1716853","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T04:08:41Z","timestamp":1753070921000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phenome\u2010Wide Mendelian Randomization and Colocalization Study Reveals Genetic Association Between PBC and Other Autoimmune Disorders"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2265-0114","authenticated-orcid":false,"given":"Shuyi","family":"Shi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3220-7925","authenticated-orcid":false,"given":"Minghui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5221-5124","authenticated-orcid":false,"given":"Haonan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1711-6347","authenticated-orcid":false,"given":"Fang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4178-4916","authenticated-orcid":false,"given":"Yuhu","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,20]]},"reference":[{"key":"e_1_2_15_1_2","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2020.0028"},{"key":"e_1_2_15_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/1751-2980.12196"},{"key":"e_1_2_15_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104537"},{"key":"e_1_2_15_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1346"},{"key":"e_1_2_15_5_2","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v12.i5.880"},{"key":"e_1_2_15_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-015-0011-z"},{"key":"e_1_2_15_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15616"},{"key":"e_1_2_15_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.791778"},{"key":"e_1_2_15_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2022.152142"},{"key":"e_1_2_15_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2024.103188"},{"key":"e_1_2_15_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0298225"},{"key":"e_1_2_15_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1264554"},{"key":"e_1_2_15_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2021-107696"},{"key":"e_1_2_15_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.04.055"},{"key":"e_1_2_15_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1974"},{"key":"e_1_2_15_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv402"},{"key":"e_1_2_15_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn564"},{"key":"e_1_2_15_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009786"},{"key":"e_1_2_15_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008601"},{"key":"e_1_2_15_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr917"},{"key":"e_1_2_15_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00913-z"},{"key":"e_1_2_15_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004383"},{"key":"e_1_2_15_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/rssb.12388"},{"key":"e_1_2_15_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0016-5085(19)30497-4"},{"key":"e_1_2_15_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/bf01311724"},{"key":"e_1_2_15_26_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.2.8182"},{"key":"e_1_2_15_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140455"},{"key":"e_1_2_15_28_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201204-0708oc"},{"key":"e_1_2_15_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01381-y"},{"key":"e_1_2_15_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2467"},{"key":"e_1_2_15_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2770"},{"key":"e_1_2_15_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds359"},{"key":"e_1_2_15_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.631"},{"key":"e_1_2_15_34_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.144576"},{"key":"e_1_2_15_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2010.36"},{"key":"e_1_2_15_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad070"},{"key":"e_1_2_15_37_2","doi-asserted-by":"publisher","DOI":"10.15403\/jgld.2014.1121.263.kus"},{"key":"e_1_2_15_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201600084"}],"container-title":["Canadian 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