A genome-wide association study identifies six novel risk loci for primary biliary cholangitis

• Published in: Nature communications Vol. 8; no. 1; p. 14828
• Main Authors: Qiu, Fang, Tang, Ruqi, Zuo, Xianbo, Shi, Xingjuan, Wei, Yiran, Zheng, Xiaodong, Dai, Yaping, Gong, Yuhua, Wang, Lan, Xu, Ping, Zhu, Xiang, Wu, Jian, Han, Chongxu, Gao, Yueqiu, Zhang, Kui, Jiang, Yuzhang, Zhou, Jianbo, Shao, Youlin, Hu, Zhigang, Tian, Ye, Zhang, Haiyan, Dai, Na, Liu, Lei, Wu, Xudong, Zhao, Weifeng, Zhang, Xiaomin, Zang, Zhidong, Nie, Jinshan, Sun, Weihao, Zhao, Yi, Mao, Yuan, Jiang, Po, Ji, Hualiang, Dong, Qing, Li, Junming, Li, Zhenzhong, Bai, Xinli, Li, Li, Lin, Maosong, Dong, Ming, Li, Jinxin, Zhu, Ping, Wang, Chan, Zhang, Yanqiu, Jiang, Peng, Wang, Yujue, Jawed, Rohil, Xu, Jing, Zhang, Yu, Wang, Qixia, Yang, Yue, Yang, Fan, Lian, Min, Jiang, Xiang, Xiao, Xiao, Li, Yanmei, Fang, Jingyuan, Qiu, Dekai, Zhu, Zhen, Qiu, Hong, Zhang, Jianqiong, Tian, Wenyan, Chen, Sufang, Jiang, Ling, Ji, Bing, Li, Ping, Chen, Guochang, Wu, Tianxue, Sun, Yan, Yu, Jianjiang, Tang, Huijun, He, Michun, Xia, Min, Pei, Hao, Huang, Lihua, Qing, Zhuye, Wu, Jianfang, Huang, Qinghai, Han, Junhai, Xie, Wei, Sun, Zhongsheng, Guo, Jian, He, Gengsheng, Eric Gershwin, M., Lian, Zhexiong, Liu, Xiang, Seldin, Michael F., Liu, Xiangdong, Chen, Weichang, Ma, Xiong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.04.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 45/43; 631/208/205/2138; 692/4020/4021/1607/1606; Adolescent; Adult; Aged; Aged, 80 and over; Asian Continental Ancestry Group; Autoimmune diseases; Autoimmune Diseases - genetics; Case-Control Studies; Child; Child, Preschool; Chinese medicine; Cholangitis; Cholangitis - genetics; Dermatology; Disease; Gastroenterology; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomes; Hepatology; Hospitals; Humanities and Social Sciences; Humans; Immunology; Laboratories; Life sciences; Middle Aged; multidisciplinary; Rheumatology; Science; Science (multidisciplinary); Young Adult; Beijing China; China
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14828

Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong hereditary component. Here, we report a genome-wide association study that included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls. Our results show genome-wide association of 14 PBC risk loci including previously identified 6p21 ( HLA-DRA and DPB1 ), 17q12 ( ORMDL3 ), 3q13.33 ( CD80 ), 2q32.3 ( STAT1 / STAT4 ), 3q25.33 ( IL12A ), 4q24 ( NF-κB ) and 22q13.1 ( RPL3 / SYNGR1 ). We also identified variants in IL21 , IL21R , CD28/CTLA4/ICOS , CD58 , ARID3A and IL16 as novel PBC risk loci. These new findings and histochemical studies showing enhanced expression of IL21 and IL21R in PBC livers (particularly in the hepatic portal tracks) support a disease mechanism in which the deregulation of the IL21 signalling pathway, in addition to CD4 T-cell activation and T-cell co-stimulation are critical components in the development of PBC. Primary biliary cholangitis is an autoimmune liver disease. Here, the authors show that variants in interleukin genes which potentially deregulate their expression are associated with this condition, and suggest that the IL21 signalling pathway may have a role in disease aetiology.