A genome-wide association study identifies six novel risk loci for primary biliary cholangitis
Open accessAbstract
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.
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The 19p13.3 locus was first reported to be associated with PBC in a Han Chinese cohort.
“We recently performed a large-scale GWAS in a Han Chinese PBC cohort and identified six novel variants associated with PBC, in which we first reported that the 19p13.3 locus was associated with PBC13.”
From A regulatory variant at 19p13.3 is associated with primary biliary cholangitis risk and ARID3A expression (2023) · cites this paper as [13]
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Self-citation
- Authors
- Qiu, F., Tang, R., Zuo, X., Shi, X., Wei, Y., Zheng, X., Dai, Y., Gong, Y., Wang, L., Xu, P., Zhu, X., Wu, J., Han, C., Gao, Y., Zhang, K., Jiang, Y., Zhou, J., Shao, Y., Hu, Z., Tian, Y., Zhang, H., Dai, N., Liu, L., Wu, X., Zhao, W., Zhang, X., Zang, Z., Nie, J., Sun, W., Zhao, Y., Mao, Y., Jiang, P., Ji, H., Dong, Q., Li, J., Li, Z., Bai, X., Li, L., Lin, M., Dong, M., Li, J., Zhu, P., Wang, C., Zhang, Y., Jiang, P., Wang, Y., Jawed, R., Xu, J., Zhang, Y., Wang, Q., Yang, Y., Yang, F., Lian, M., Jiang, X., Xiao, X., Li, Y., Fang, J., Qiu, D., Zhu, Z., Qiu, H., Zhang, J., Tian, W., Chen, S., Jiang, L., Ji, B., Li, P., Chen, G., Wu, T., Sun, Y., Yu, J., Tang, H., He, M., Xia, M., Pei, H., Huang, L., Qing, Z., Wu, J., Huang, Q., Han, J., Xie, W., Sun, Z., Guo, J., He, G., Eric Gershwin, M., Lian, Z., Liu, X., Seldin, M. F., Liu, X., Chen, W., & Ma, X.
- Affiliations
- Southeast University (CN)
- Shanghai Jiao Tong University (CN)
- Anhui Medical University (CN)
- 81th Hospital of PLA (CN)
- Soochow University (CN)
- Traditional Chinese Medicine Hospital of Kunshan (CN)
- Yangzhou University (CN)
- Shanghai University of Traditional Chinese Medicine (CN)
- Nanjing Drum Tower Hospital (CN)
- Huaian First People’s Hospital (CN)
- Jiangyin People's Hospital (CN)
- Changzhou Third People's Hospital (CN)
- Wuxi People's Hospital (CN)
- Second Affiliated Hospital of Soochow University (CN)
- Jiangsu University (CN)
- Yixing People's Hospital (CN)
- Yancheng First People's Hospital (CN)
- First Affiliated Hospital of Soochow University (CN)
- Nanjing Second Hospital (CN)
- Eastern Hepatobiliary Surgery Hospital (CN)
- Hainan Medical University (CN)
- Nantong University (CN)
- Suzhou Traditional Chinese Medicine Hospital (CN)
- Beijing Hospital (CN)
- Second Hospital of Hebei Medical University (CN)
- Zhongda Hospital Southeast University (CN)
- The Affiliated Taizhou People's Hospital of Nanjing Medical University (CN)
- Chinese Academy of Sciences (CN)
- Fudan University (CN)
- University of California, Davis (US)
- University of Science and Technology of China (CN)
- Corresponding author
- Liu, Xiang
- Liu, Xiangdong
- Chen, Weichang
- Ma, Xiong
- ORCID
- Qiu, Fang
- Tang, Ruqi
- Zuo, Xianbo
- Shi, Xingjuan
- Wei, Yiran
- Zheng, Xiaodong
- Dai, Yaping
- Gong, Yuhua
- Xu, Ping
- Wu, Jian
- Gao, Yueqiu
- Jiang, Yuzhang
- Zhou, Jianbo
- Shao, Youlin
- Hu, Zhigang
- Tian, Ye
- Zhang, Haiyan
- Dai, Na
- Liu, Lei
- Wu, Xudong
- Zhao, Weifeng
- Zhang, Xiaomin
- Zang, Zhidong
- Zhao, Yi
- Mao, Yuan
- Li, Junming
- Li, Zhenzhong
- Li, Jinxin
- Zhu, Ping
- Wang, Chan
- Xu, Jing
- Zhang, Yu
- Wang, Qixia
- Yang, Fan
- Lian, Min
- Jiang, Xiang
- Xiao, Xiao
- Li, Yanmei
- Zhu, Zhen
- Zhang, Jianqiong
- Ji, Bing
- Li, Ping
- Chen, Guochang
- Xia, Min
- Huang, Lihua
- Wu, Jianfang
- Han, Junhai
- Xie, Wei
- Guo, Jian
- He, Gengsheng
- Liu, Xiang
- Chen, Weichang
- Ma, Xiong
- Venue
- Nature Communications
- Published
- 2017-04-20
- Volume
- 8
- Issue
- 1
- Pages
- 14828-14828
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5429142
- OpenAlex
- W2605875188
- Cited by
- 140
- References
- 44
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 20 · 2023: 20 · 2022: 18 · 2021: 15 · 2020: 19 · 2019: 17 · 2018: 15 · 2017: 2
- FWCI
- 8.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (#81400608, 81430034, 91542123, 81272737, 81570469, 81620108002, 81130058, 81270295, 81325002, 31301113)
- Government of Jiangsu Province
- Ministry of Education, Science and Technology
- Natural Science Foundation of Jiangsu Province (SBK2015020697, BK20130607)
- Shanghai Jiao Tong University (YG2014MS43)
- National Institutes of Health
- Collaborative Innovation Center for Cardiovascular Disease Translational Medicine
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK091823)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Keywords
- primary biliary cirrhosis, genetic susceptibility loci, autoimmune liver disease, IL-21, interleukin-21 receptor, CD58, ARID3A, interleukin-16, HLA-DRA, DPB1, ORMDL3, CD80, IL12A, NF-κB, T cell costimulation, CD4+ T cell activation, Han Chinese
- MeSH terms
- Ribosomal Protein L3, Adolescent, Adult, Aged, Aged, 80 and over, Autoimmune Diseases, Child, Child, Preschool, Cholangitis, Humans, Middle Aged, Case-Control Studies, Genetic Predisposition to Disease, Asian People, Genome-Wide Association Study, Young Adult
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