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A genome-wide association study identifies six novel risk loci for primary biliary cholangitis
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 co...
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group
2017
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429142/ https://www.ncbi.nlm.nih.gov/pubmed/28425483 http://dx.doi.org/10.1038/ncomms14828 |
| _version_ | 1783235971313041408 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Qiu, Fang |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-5429142 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-54291422017-05-24 A genome-wide association study identifies six novel risk loci for primary biliary cholangitis 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 Nat Commun Article 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. Nature Publishing Group 2017-04-20 /pmc/articles/PMC5429142/ /pubmed/28425483 http://dx.doi.org/10.1038/ncomms14828 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| spellingShingle | Article 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 A genome-wide association study identifies six novel risk loci for primary biliary cholangitis |
| title | A genome-wide association study identifies six novel risk loci for primary biliary cholangitis |
| title_full | A genome-wide association study identifies six novel risk loci for primary biliary cholangitis |
| title_fullStr | A genome-wide association study identifies six novel risk loci for primary biliary cholangitis |
| title_full_unstemmed | A genome-wide association study identifies six novel risk loci for primary biliary cholangitis |
| title_short | A genome-wide association study identifies six novel risk loci for primary biliary cholangitis |
| title_sort | genome-wide association study identifies six novel risk loci for primary biliary cholangitis |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429142/ https://www.ncbi.nlm.nih.gov/pubmed/28425483 http://dx.doi.org/10.1038/ncomms14828 |
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