{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:47:39Z","timestamp":1789192059675,"version":"build-2803163510"},"reference-count":83,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K08065"],"award-info":[{"award-number":["22K08065"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K08413"],"award-info":[{"award-number":["19K08413"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17H04169"],"award-info":[{"award-number":["17H04169"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Research from the NHO","award":["22K08065"],"award-info":[{"award-number":["22K08065"]}]},{"name":"Clinical Research from the NHO","award":["19K08413"],"award-info":[{"award-number":["19K08413"]}]},{"name":"Clinical Research from the NHO","award":["17H04169"],"award-info":[{"award-number":["17H04169"]}]},{"name":"Ministry of Health, Labour, and Welfare of Japan","award":["22K08065"],"award-info":[{"award-number":["22K08065"]}]},{"name":"Ministry of Health, Labour, and Welfare of Japan","award":["19K08413"],"award-info":[{"award-number":["19K08413"]}]},{"name":"Ministry of Health, Labour, and Welfare of Japan","award":["17H04169"],"award-info":[{"award-number":["17H04169"]}]},{"name":"Takeda Foundation","award":["22K08065"],"award-info":[{"award-number":["22K08065"]}]},{"name":"Takeda Foundation","award":["19K08413"],"award-info":[{"award-number":["19K08413"]}]},{"name":"Takeda Foundation","award":["17H04169"],"award-info":[{"award-number":["17H04169"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease in which the small intrahepatic bile ducts are destroyed by autoimmune reactions. Among autoimmune diseases, which are polygenic complex traits caused by the combined contribution of genetic and environmental factors, PBC exhibits the strongest involvement of genetic heritability in disease development. As at December 2022, genome-wide association studies (GWASs) and associated meta-analyses identified approximately 70 PBC susceptibility gene loci in various populations, including those of European and East Asian descent. However, the molecular mechanisms through which these susceptibility loci affect the pathogenesis of PBC are not fully understood. This study provides an overview of current data regarding the genetic factors of PBC as well as post-GWAS approaches to identifying primary functional variants and effector genes in disease-susceptibility loci. Possible mechanisms of these genetic factors in the development of PBC are also discussed, focusing on four major disease pathways identified by in silico gene set analyses, namely, (1) antigen presentation by human leukocyte antigens, (2) interleukin-12-related pathways, (3) cellular responses to tumor necrosis factor, and (4) B cell activation, maturation, and differentiation pathways.<\/jats:p>","DOI":"10.3390\/genes14020405","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T04:08:07Z","timestamp":1675656487000},"page":"405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update"],"prefix":"10.3390","volume":"14","author":[{"given":"Yuki","family":"Hitomi","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, 2-1001-1 Kubara, Omura 856-8562, Japan"},{"name":"Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 2-1001-1 Kubara, Omura 856-8562, Japan"},{"name":"Headquarters of PBC Research in NHO Study Group for Liver Disease in Japan (NHOSLJ), Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, 2-1001-1 Kubara, Omura 856-8562, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1084\/jem.181.5.1835","article-title":"HLA DRB4 0101-restricted immunodominant T cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis: Evidence of molecular mimicry in human autoimmune diseases","volume":"181","author":"Shimoda","year":"1995","journal-title":"J. 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