The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update

Hitomi, Yuki; Nakamura, Minoru

doi:10.3390/genes14020405

Cited by 26Liver Diseases and ImmunityGenetic Associations and EpidemiologyPediatric Hepatobiliary Diseases and Treatments

The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update

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Hitomi, Yuki, Nakamura, Minoru·2023·Genes

DOI 10.3390/genes14020405PMC PMC9957238

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Abstract

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.

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Characteristic HLA regions linked to primary biliary cholangitis susceptibility include HLA class 2 alleles, principally HLA-DRB6, HLA-DQA2, and HLA-DRB1.
“Characteristic HLA regions linked to primary biliary cholangitis susceptibility include HLA class 2 alleles, principally HLA-DRB6, HLA-DQA2, and HLA-DRB1.11”
From Primary biliary cholangitis. (2024) · cites this paper as [11]
Section 2.1 (page not provided) links HLA class II alleles to PBC susceptibility and identifies predisposing HLA-DRB1 alleles. It does not identify HLA-DRB6 or HLA-DQA2 as susceptibility alleles; it names HLA-DQA1 and HLA-DQB1 alleles instead. (LLM, conf=0.88)
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[41]Kawashima M. Hitomi Y. Aiba Y. Nishida N. Kojima K. Kawai Y. Nakamura H. Tanaka A. Zeniya M. Hashimoto E. Genome-wide association study identified PRKCB as a genetic susceptibility locus for primary biliary cholangitis in a Japanese population Hum. Mol. Genet. 2017 26 650 659 28062665

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Authors: Hitomi, Y., & Nakamura, M.
Affiliations: National Center for Global Health and Medicine (JP)
Nagasaki Medical Center (JP)
Corresponding author: Hitomi, Yuki
ORCID: Hitomi, Yuki
Venue: Genes
Publisher: MDPI AG
Published: 2023-02-03
Volume: 14
Issue: 2
Pages: 405
ISSN: 2073-4425 (ISSN-L)
DOI: 10.3390/genes14020405
PMC: PMC9957238
OpenAlex: W4319317419
Cited by: 26
References: 87
Citations by year: 2026: 6 · 2025: 7 · 2024: 9 · 2023: 4
FWCI: 1.12
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Genes (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Japan Society for the Promotion of Science (22K08065, 19K08413, 17H04169)
Clinical Research from the NHO (22K08065, 19K08413, 17H04169)
Ministry of Health, Labour, and Welfare of Japan (22K08065, 19K08413, 17H04169)
Takeda Foundation (22K08065, 19K08413, 17H04169)
Topics: Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
Keywords: primary biliary cirrhosis, genetic susceptibility, genetic susceptibility loci, autoimmune liver disease, B cell activation, pathogenesis, functional variants, gene set analysis
MeSH terms: Autoimmune Diseases, Cell Differentiation, Humans, Liver Cirrhosis, Biliary, Tumor Necrosis Factor-alpha, Genome-Wide Association Study

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The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update

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