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

Author

Listed:
  • Fang Qiu

    (Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University)

  • Ruqi Tang

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

  • Xianbo Zuo

    (Institute of Dermatology, Anhui Medical University)

  • Xingjuan Shi

    (Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University)

  • Yiran Wei

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

  • Xiaodong Zheng

    (Institute of Dermatology, Anhui Medical University)

  • Yaping Dai

    (The Fifth People’s Hospital of Wuxi)

  • Yuhua Gong

    (The Third People’s Hospital of Zhenjiang)

  • Lan Wang

    (The 81th Hospital of PLA)

  • Ping Xu

    (The Fifth People’s Hospital of Suzhou, Soochow University)

  • Xiang Zhu

    (The Fifth People’s Hospital of Suzhou, Soochow University)

  • Jian Wu

    (The First Affiliated Hospital of Soochow University)

  • Chongxu Han

    (Subei People’s Hospital, Clinical Medical College, Yangzhou University)

  • Yueqiu Gao

    (Shuguang Hospital, Shanghai University of Traditional Chinese Medicine)

  • Kui Zhang

    (Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School)

  • Yuzhang Jiang

    (Huai’an First People’s Hospital, Nanjing Medical University)

  • Jianbo Zhou

    (Jiangyin People’s Hospital, Southeast University)

  • Youlin Shao

    (The Third People’s Hospital of Changzhou)

  • Zhigang Hu

    (Affiliated Wuxi People’s Hospital of Nanjing Medical University)

  • Ye Tian

    (The Second Affiliated Hospital of Soochow University)

  • Haiyan Zhang

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

  • Na Dai

    (Jiangsu University affiliated Kunshan Hospital)

  • Lei Liu

    (Yixing People’s Hospital)

  • Xudong Wu

    (Yancheng First People’s Hospital)

  • Weifeng Zhao

    (The First Affiliated Hospital of Soochow University)

  • Xiaomin Zhang

    (The University Hospital, Southeast University)

  • Zhidong Zang

    (The Second Hospital of Nanjing, Southeast University)

  • Jinshan Nie

    (Taicang First People’s Hospital, Soochow University)

  • Weihao Sun

    (The First Affiliated Hospital of Nanjing Medical University)

  • Yi Zhao

    (Eastern Hepatobiliary Surgery Hospital)

  • Yuan Mao

    (Nanjing Kingmed Clinical Laboratory Co. Ltd.)

  • Po Jiang

    (The Second People’s Hospital of Jingjiang)

  • Hualiang Ji

    (Hai’an People’s Hospital, Nantong University Medical School)

  • Qing Dong

    (Suzhou Hospital of Traditional Chinese Medicine)

  • Junming Li

    (The First Affiliated Hospital of Nanchang University)

  • Zhenzhong Li

    (The Second Hospital of Hebei Medical University)

  • Xinli Bai

    (Zhongda Hospital, School of Medicine, Southeast University)

  • Li Li

    (Taizhou People’s Hospital)

  • Maosong Lin

    (Traditional Chinese Medicine Hospital of Kunshan)

  • Ming Dong

    (Beijing Institutes of Life Science, Chinese Academy of Sciences)

  • Jinxin Li

    (Beijing Hospital)

  • Ping Zhu

    (School of Public Health, Fudan University)

  • Chan Wang

    (Allergy, and Clinical Immunology, Rowe Program in Genetics, University of California-Davis)

  • Yanqiu Zhang

    (School of Life Sciences, University of Science and Technology of China)

  • Peng Jiang

    (The First Affiliated Hospital, Hainan Medical University)

  • Yujue Wang

    (Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University)

  • Rohil Jawed

    (Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University)

  • Jing Xu

    (Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University)

  • Yu Zhang

    (Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University)

  • Qixia Wang

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

  • Yue Yang

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

  • Fan Yang

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

  • Min Lian

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

  • Xiang Jiang

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

  • Xiao Xiao

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

  • Yanmei Li

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

  • Jingyuan Fang

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

  • Dekai Qiu

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

  • Zhen Zhu

    (The Third People’s Hospital of Changzhou)

  • Hong Qiu

    (The 81th Hospital of PLA)

  • Jianqiong Zhang

    (Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University)

  • Wenyan Tian

    (The First Affiliated Hospital of Soochow University)

  • Sufang Chen

    (The Fifth People’s Hospital of Suzhou, Soochow University)

  • Ling Jiang

    (The First Affiliated Hospital of Soochow University)

  • Bing Ji

    (The 81th Hospital of PLA)

  • Ping Li

    (The 81th Hospital of PLA)

  • Guochang Chen

    (Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School)

  • Tianxue Wu

    (Subei People’s Hospital, Clinical Medical College, Yangzhou University)

  • Yan Sun

    (Subei People’s Hospital, Clinical Medical College, Yangzhou University)

  • Jianjiang Yu

    (Jiangyin People’s Hospital, Southeast University)

  • Huijun Tang

    (Jiangyin People’s Hospital, Southeast University)

  • Michun He

    (The First Affiliated Hospital of Soochow University)

  • Min Xia

    (Affiliated Wuxi People’s Hospital of Nanjing Medical University)

  • Hao Pei

    (The Fifth People’s Hospital of Wuxi)

  • Lihua Huang

    (The Fifth People’s Hospital of Wuxi)

  • Zhuye Qing

    (Nanjing Kingmed Clinical Laboratory Co. Ltd.)

  • Jianfang Wu

    (Traditional Chinese Medicine Hospital of Kunshan)

  • Qinghai Huang

    (Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University)

  • Junhai Han

    (Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University)

  • Wei Xie

    (Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University)

  • Zhongsheng Sun

    (Beijing Institutes of Life Science, Chinese Academy of Sciences)

  • Jian Guo

    (Beijing Hospital)

  • Gengsheng He

    (School of Public Health, Fudan University)

  • M. Eric Gershwin

    (Allergy, and Clinical Immunology, Rowe Program in Genetics, University of California-Davis)

  • Zhexiong Lian

    (School of Life Sciences, University of Science and Technology of China)

  • Xiang Liu

    (The First Affiliated Hospital, Hainan Medical University)

  • Michael F. Seldin

    (Allergy, and Clinical Immunology, Rowe Program in Genetics, University of California-Davis)

  • Xiangdong Liu

    (Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University)

  • Weichang Chen

    (The First Affiliated Hospital of Soochow University)

  • Xiong Ma

    (Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease)

Abstract

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.

Suggested Citation

  • Fang Qiu & Ruqi Tang & Xianbo Zuo & Xingjuan Shi & Yiran Wei & Xiaodong Zheng & Yaping Dai & Yuhua Gong & Lan Wang & Ping Xu & Xiang Zhu & Jian Wu & Chongxu Han & Yueqiu Gao & Kui Zhang & Yuzhang Jian, 2017. "A genome-wide association study identifies six novel risk loci for primary biliary cholangitis," Nature Communications, Nature, vol. 8(1), pages 1-8, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14828
    DOI: 10.1038/ncomms14828
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    Citations

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    Cited by:

    1. You Li & Zhiqiang Li & Ruiling Chen & Min Lian & Hanxiao Wang & Yiran Wei & Zhengrui You & Jun Zhang & Bo Li & Yikang Li & Bingyuan Huang & Yong Chen & Qiaoyan Liu & Zhuwan Lyu & Xueying Liang & Qi Mi, 2023. "A regulatory variant at 19p13.3 is associated with primary biliary cholangitis risk and ARID3A expression," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Younghun Han & Jinyoung Byun & Catherine Zhu & Ryan Sun & Julia Y. Roh & Heather J. Cordell & Hyun-Sung Lee & Vikram R. Shaw & Sung Wook Kang & Javad Razjouyan & Matthew A. Cooley & Manal M. Hassan & , 2023. "Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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