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

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 facto...

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Bibliographic Details
Published in:Genes 2023-02, Vol.14 (2), p.405
Main Authors: Hitomi, Yuki, Nakamura, Minoru
Format: Article
Language:English
Subjects:
Antibodies
Antigen presentation
Antigens
Autoimmune diseases
Bile ducts
Cell activation
Cell differentiation
Cholangitis
Coronaviruses
COVID-19
Disease
Environmental factors
Gene loci
Genetic aspects
Genetic factors
Genome-wide association studies
Genomes
Hepatitis
Heritability
Interleukin 12
Liver diseases
Lymphocytes
Molecular modelling
Pathogenesis
Polygenic inheritance
Review
Severe acute respiratory syndrome coronavirus 2
Signal transduction
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Summary: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.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes14020405