A genome-wide association study identifies six novel risk loci for primary biliary cholangitis.
Fang QiuRuqi TangXianbo ZuoXingjuan ShiYiran WeiXiaodong ZhengYaping DaiYuhua GongLan WangPing XuXiang ZhuJian WuChongxu HanYueqiu GaoKui ZhangYuzhang JiangJianbo ZhouYoulin ShaoZhigang HuYe TianHaiyan ZhangNa DaiLei LiuXudong WuWeifeng ZhaoXiaomin ZhangZhidong ZangJinshan NieWeihao SunYi ZhaoYuan MaoPo JiangHualiang JiQing DongJunming LiZhenzhong LiXinli BaiLi LiMaosong LinMing DongJinxin LiPing ZhuChan WangYanqiu ZhangPeng JiangYujue WangRohil JawedJing XuYu ZhangQixia WangYue YangFan YangMin LianXiang JiangXiao XiaoYanmei LiJingyuan FangDekai QiuZhen ZhuHong QiuJianqiong ZhangWenyan TianSufang ChenLing JiangBing JiPing LiGuochang ChenTianxue WuYan SunJianjiang YuHuijun TangMichun HeMin XiaHao PeiLihua HuangZhuye QingJianfang WuQinghai HuangJunhai HanWei XieZhongsheng SunJian GuoGengsheng HeM Eric GershwinZhexiong LianXiang LiuMichael F SeldinXiangdong LiuWeichang ChenXiong MaPublished in: Nature communications (2017)
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.