title: Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese.
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.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Si
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Guangzhou 510060, China.
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Bei
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Bobo
authors.initials: B
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Song
authors.affiliation: Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Zhiyu
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authors.lastname: Bao
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Han
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Chengming
authors.initials: C
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Tu
authors.affiliation: Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Liang
authors.affiliation: Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Infectious Disease, Affiliated You'an Hospital, Capital University of Medical Science, Beijing 100069, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Huifen
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: BGI-Shenzhen, Shenzhen 518031, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: He
authors.affiliation: BGI-Shenzhen, Shenzhen 518031, China.
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Clinical School of Nanjing University, Nanjing 210002, China.
authors.forename: Xiaobing
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authors.lastname: Xu
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Clinical School of Nanjing University, Nanjing 210002, China.
authors.forename: Hongzan
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authors.lastname: Ji
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310006, China.
authors.forename: Chaohui
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Hepatobiliary Surgery I, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Hepatobiliary Surgery I, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Baocai
authors.initials: B
authors.lastname: Xing
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Xiaobo
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authors.lastname: Yang
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Tan
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Guangzhou 510060, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Oncology in Southern China, Guangzhou 510060, China.
authors.forename: Shengping
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in Southern China, Guangzhou 510060, China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.affiliation: Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Zengnan
authors.initials: Z
authors.lastname: Mo
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.|National Engineering Research Center for Protein Drugs, Beijing 100850, China.|National Center for Protein Sciences at Beijing, Beijing 100850, China.
authors.forename: Gangqiao
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002460:Cell Line; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006514:Hepatitis B Surface Antigens / Q000302:isolation & purification; D006515:Hepatitis B virus / Q000302:isolation & purification / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000821:virology; D022781:Hepatocytes; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012698:Serologic Tests; D019562:Viral Load / Q000276:immunology; D014779:Virus Replication / Q000276:immunology; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D006514:Hepatitis B Surface Antigens; C000618262:INTS10 protein, human; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3