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; Gangqiao Zhou

doi:10.1038/ncomms11664

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

Nat Commun. 2016 May 31:7:11664. doi: 10.1038/ncomms11664.

Authors

Yuanfeng Li^{1

2

3}, Lanlan Si^{1

2

3}, Yun Zhai^{1

2

3}, Yanling Hu⁴, Zhibin Hu⁵, Jin-Xin Bei⁶, Bobo Xie^{1

2

3}, Qian Ren^{1

2

3}, Pengbo Cao^{1

2

3}, Fei Yang^{1

2

3}, Qingfeng Song⁷, Zhiyu Bao⁷, Haitao Zhang^{1

2

3}, Yuqing Han^{1

2

3}, Zhifu Wang^{1

2

3}, Xi Chen^{1

2

3}, Xia Xia^{1

2

3}, Hongbo Yan^{1

2

3}, Rui Wang^{1

2

3}, Ying Zhang^{1

2

3}, Chengming Gao^{1

2

3}, Jinfeng Meng^{1

2

3}, Xinyi Tu^{1

2

3}, Xinqiang Liang⁷, Ying Cui⁷, Ying Liu⁸, Xiaopan Wu⁸, Zhuo Li⁹, Huifen Wang¹⁰, Zhaoxia Li¹¹, Bo Hu¹¹, Minghui He¹², Zhibo Gao¹², Xiaobing Xu¹³, Hongzan Ji¹³, Chaohui Yu¹⁴, Yi Sun¹⁵, Baocai Xing¹⁵, Xiaobo Yang⁴, Haiying Zhang⁴, Aihua Tan⁴, Chunlei Wu⁴, Weihua Jia⁶, Shengping Li⁶, Yi-Xin Zeng⁶, Hongbing Shen⁵, Fuchu He^{1

2

3}, Zengnan Mo⁴, Hongxing Zhang^{1

2

3}, Gangqiao Zhou^{1

2

3}

Affiliations

¹ State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
² National Engineering Research Center for Protein Drugs, Beijing 100850, China.
³ National Center for Protein Sciences at Beijing, Beijing 100850, China.
⁴ Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China.
⁵ Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
⁶ State Key Laboratory of Oncology in Southern China, Guangzhou 510060, China.
⁷ Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
⁸ National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
⁹ Department of Infectious Disease, Affiliated You'an Hospital, Capital University of Medical Science, Beijing 100069, China.
¹⁰ Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing 100039, China.
¹¹ Department of Clinical Laboratory, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
¹² BGI-Shenzhen, Shenzhen 518031, China.
¹³ Department of Gastroenterology and Hepatology, Jinling Hospital, Clinical School of Nanjing University, Nanjing 210002, China.
¹⁴ Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310006, China.
¹⁵ Department of Hepatobiliary Surgery I, Peking University Cancer Hospital and Institute, Beijing 100142, China.

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.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Asian People / genetics
Carrier Proteins / genetics*
Carrier Proteins / immunology
Case-Control Studies
Cell Line
Chromosomes, Human, Pair 8 / genetics*
Female
Genetic Loci / genetics
Genetic Predisposition to Disease*
Genome-Wide Association Study
Hepatitis B Surface Antigens / isolation & purification
Hepatitis B virus / isolation & purification
Hepatitis B virus / physiology*
Hepatitis B, Chronic / blood
Hepatitis B, Chronic / genetics*
Hepatitis B, Chronic / immunology
Hepatitis B, Chronic / virology
Hepatocytes
Humans
Interferon Regulatory Factor-3 / immunology
Interferon Regulatory Factor-3 / metabolism
Liver / cytology
Liver / immunology
Liver / virology
Male
Middle Aged
Polymorphism, Single Nucleotide
Serologic Tests
Viral Load / immunology
Virus Replication / immunology
Young Adult

Substances

Carrier Proteins
Hepatitis B Surface Antigens
INTS10 protein, human
IRF3 protein, human
Interferon Regulatory Factor-3

Grants and funding

U24 AA022002/AA/NIAAA NIH HHS/United States