The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update.
The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update.
复制标题
DOI：
10.3390/genes14020405
复制
发表时间：
2023-02-03
期刊：
影响因子：
3.5
通讯作者：
Nakamura, Minoru
中科院分区：
文献类型：
--
作者：
Hitomi, Yuki;Nakamura, Minoru
关键词：
原发性胆管炎（PBC）是一种慢性进行性胆汁淤积性肝病，其自身免疫反应破坏肝内小胆管。自身免疫性疾病是由遗传和环境因素共同作用引起的多基因复杂性状，其中PBC在疾病发展中表现出最强的遗传参与。截至2022年12月，全基因组关联研究（GWASs）和相关的荟萃分析在包括欧洲和东亚后裔在内的各种人群中确定了大约70个PBC易感基因位点。然而，这些易感位点影响PBC发病机制的分子机制尚不完全清楚。本研究概述了关于PBC遗传因素的当前数据，以及gwas后识别疾病易感位点主要功能变异和效应基因的方法。本文还讨论了这些遗传因素在PBC发展中的可能机制，重点讨论了通过硅基因集分析确定的四种主要疾病途径，即(1)人类白细胞抗原的抗原呈递，(2)白细胞介素-12相关途径，(3)肿瘤坏死因子的细胞反应，以及(4)B细胞活化、成熟和分化途径。
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.
登录
查看更多内容
影响因子：
25.7
作者：
Cordell HJ;Fryett JJ;Ueno K;Darlay R;Aiba Y;Hitomi Y;Kawashima M;Nishida N;Khor SS;Gervais O;Kawai Y;Nagasaki M;Tokunaga K;Tang R;Shi Y;Li Z;Juran BD;Atkinson EJ;Gerussi A;Carbone M;Asselta R;Cheung A;de Andrade M;Baras A;Horowitz J;Ferreira MAR;Sun D;Jones DE;Flack S;Spicer A;Mulcahy VL;Byan J;Han Y;Sandford RN;Lazaridis KN;Amos CI;Hirschfield GM;Seldin MF;Invernizzi P;Siminovitch KA;Ma X;Nakamura M;Mells GF;PBC Consortia;Canadian PBC Consortium;Chinese PBC Consortium;Italian PBC Study Group;Japan-PBC-GWAS Consortium;US PBC Consortium;UK-PBC Consortium
通讯作者：
UK-PBC Consortium
影响因子：
5.2
作者：
Davis RS
通讯作者：
Davis RS
影响因子：
16.6
作者：
Cordell HJ;Han Y;Mells GF;Li Y;Hirschfield GM;Greene CS;Xie G;Juran BD;Zhu D;Qian DC;Floyd JA;Morley KI;Prati D;Lleo A;Cusi D;Canadian-US PBC Consortium;Italian PBC Genetics Study Group;UK-PBC Consortium;Gershwin ME;Anderson CA;Lazaridis KN;Invernizzi P;Seldin MF;Sandford RN;Amos CI;Siminovitch KA
通讯作者：
Siminovitch KA
影响因子：
64.8
作者：
COVID-19 Host Genetics Initiative
通讯作者：
COVID-19 Host Genetics Initiative
影响因子：
13.5
作者：
Bae, Heekyong R.;Leung, Patrick S. C.;Tsuneyama, Koichi;Valencia, Julio C.;Hodge, Deborah L.;Kim, Seohyun;Back, Tim;Karwan, Megan;Merchant, Anand S.;Baba, Nobuyuki;Feng, Dechun;Park, Ogyi;Gao, Bin;Yang, Guo-Xiang;Gershwin, M. Eric;Young, Howard A.
通讯作者：
Young, Howard A.