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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MDPI AG
2023-02-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/2/405 |
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| author | Yuki Hitomi Minoru Nakamura |
| author_facet | Yuki Hitomi Minoru Nakamura |
| author_sort | Yuki Hitomi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T08:47:25Z |
| format | Article |
| id | doaj.art-ea71ed7b40644b15b6c51f10fc10630c |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T08:47:25Z |
| publishDate | 2023-02-01 |
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| series | Genes |
| spelling | doaj.art-ea71ed7b40644b15b6c51f10fc10630c2023-11-16T20:42:31ZengMDPI AGGenes2073-44252023-02-0114240510.3390/genes14020405The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS UpdateYuki Hitomi0Minoru Nakamura1Department of Human Genetics, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, JapanClinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, 2-1001-1 Kubara, Omura 856-8562, JapanPrimary 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.https://www.mdpi.com/2073-4425/14/2/405primary biliary cholangitis (PBC)organ-specific autoimmune diseasepolygenic complex traitgenetic factorgenome-wide association study (GWAS)disease susceptibility gene |
| spellingShingle | Yuki Hitomi Minoru Nakamura The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update Genes primary biliary cholangitis (PBC) organ-specific autoimmune disease polygenic complex trait genetic factor genome-wide association study (GWAS) disease susceptibility gene |
| title | The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update |
| title_full | The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update |
| title_fullStr | The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update |
| title_full_unstemmed | The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update |
| title_short | The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update |
| title_sort | genetics of primary biliary cholangitis a gwas and post gwas update |
| topic | primary biliary cholangitis (PBC) organ-specific autoimmune disease polygenic complex trait genetic factor genome-wide association study (GWAS) disease susceptibility gene |
| url | https://www.mdpi.com/2073-4425/14/2/405 |
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