Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese

Yuanfeng Li, Lanlan Si, Yun Zhai, Yanling Hu, Zhibin Hu, Jin-Xin Bei, Bobo Xie, Qian Ren, Pengbo Cao, Fei Yang, Qingfeng Song, Zhiyu Bao, Haitao Zhang, Yuqing Han, Zhifu Wang, Xi Chen, Xia Xia, Hongbo Yan, Rui Wang, Ying Zhang, Chengming Gao, Jinfeng Meng, Xinyi Tu, Xinqiang Liang, Ying Cui, Ying Liu, Xiaopan Wu, Zhuo Li, Huifen Wang, Zhaoxia Li, Bo Hu, Minghui He, Zhibo Gao, Xiaobing Xu, Hongzan Ji, Chaohui Yu, Yi Sun, Baocai Xing, Xiaobo Yang, Haiying Zhang, Aihua Tan, Chunlei Wu, Weihua Jia, Shengping Li, Yi-Xin Zeng, Hongbing Shen, Fuchu He, Zengnan Mo (), Hongxing Zhang () and Gangqiao Zhou ()
Additional contact information
Yuanfeng Li: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Lanlan Si: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Yun Zhai: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Yanling Hu: Center for Genomic and Personalized Medicine, Guangxi Medical University
Zhibin Hu: MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University
Jin-Xin Bei: State Key Laboratory of Oncology in Southern China
Bobo Xie: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Qian Ren: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Pengbo Cao: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Fei Yang: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Qingfeng Song: Affiliated Cancer Hospital of Guangxi Medical University
Zhiyu Bao: Affiliated Cancer Hospital of Guangxi Medical University
Haitao Zhang: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Yuqing Han: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Zhifu Wang: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Xi Chen: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Xia Xia: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Hongbo Yan: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Rui Wang: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Ying Zhang: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Chengming Gao: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Jinfeng Meng: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Xinyi Tu: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Xinqiang Liang: Affiliated Cancer Hospital of Guangxi Medical University
Ying Cui: Affiliated Cancer Hospital of Guangxi Medical University
Ying Liu: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences
Xiaopan Wu: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences
Zhuo Li: Affiliated You’an Hospital, Capital University of Medical Science
Huifen Wang: Liver Failure Treatment and Research Center
Zhaoxia Li: the Third Affiliated Hospital, Sun Yat-sen University
Bo Hu: the Third Affiliated Hospital, Sun Yat-sen University
Minghui He: BGI-Shenzhen
Zhibo Gao: BGI-Shenzhen
Xiaobing Xu: Jinling Hospital, Clinical School of Nanjing University
Hongzan Ji: Jinling Hospital, Clinical School of Nanjing University
Chaohui Yu: the First Affiliated Hospital, College of Medicine, Zhejiang University
Yi Sun: Peking University Cancer Hospital and Institute
Baocai Xing: Peking University Cancer Hospital and Institute
Xiaobo Yang: Center for Genomic and Personalized Medicine, Guangxi Medical University
Haiying Zhang: Center for Genomic and Personalized Medicine, Guangxi Medical University
Aihua Tan: Center for Genomic and Personalized Medicine, Guangxi Medical University
Chunlei Wu: Center for Genomic and Personalized Medicine, Guangxi Medical University
Weihua Jia: State Key Laboratory of Oncology in Southern China
Shengping Li: State Key Laboratory of Oncology in Southern China
Yi-Xin Zeng: State Key Laboratory of Oncology in Southern China
Hongbing Shen: MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University
Fuchu He: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Zengnan Mo: Center for Genomic and Personalized Medicine, Guangxi Medical University
Hongxing Zhang: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine
Gangqiao Zhou: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract Hepatitis B virus (HBV) infection is a common infectious disease. Here we perform a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci involved in persistent HBV infection. GWAS scan is performed in 1,251 persistently HBV infected subjects (PIs, cases) and 1,057 spontaneously recovered subjects (SRs, controls), followed by replications in four independent populations totally consisting of 3,905 PIs and 3,356 SRs. We identify a novel locus at 8p21.3 (index rs7000921, odds ratio=0.78, P=3.2 × 10−12). Furthermore, we identify significant expression quantitative trait locus associations for INTS10 gene at 8p21.3. We demonstrate that INST10 suppresses HBV replication via IRF3 in liver cells. In clinical plasma samples, we confirm that INST10 levels are significantly decreased in PIs compared with SRs, and negatively correlated with the HBV load. These findings highlight a novel antiviral gene INTS10 at 8p21.3 in the clearance of HBV infection.

Date: 2016
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DOI: 10.1038/ncomms11664

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