Open AccessGenome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese
Author(s) -
Yuanfeng Li,
Si Lanlan,
Yun Zhai,
Yanling Hu,
Zhibin Hu,
Jin Xin Bei,
Bobo Xie,
Qian Ren,
Pengbo Cao,
Fei Yang,
Qingfeng Song,
Zhiyu Bao,
Haitao Zhang,
Yaling Han,
Zhifu Wang,
Xi Chen,
Xia Xia,
Huiwen Yan,
Rui Wang,
Ying Zhang,
Chengming Gao,
Jinfeng Meng,
Xinyi Tu,
Xiaofeng Liang,
Ying Cui,
Ying Li,
Xiaopan Wu,
Zhuo Li,
Huifen Wang,
Zhaoxia Li,
Bo Hu,
Minghui He,
Zhibo Gao,
Xinsheng Xü,
Hanxu Ji,
Chaohui Yu,
Sun Yi,
Baocai Xing,
Xiaobo Yang,
Haiying Zhang,
Aihua Tan,
Chunlei Wu,
WeiHua Jia,
Shengping Li,
Yi Zeng,
Hongbing Shen,
Fuchu He,
Zengnan Mo,
Hongxing Zhang,
Gangqiao Zhou
Publication year - 2016
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms11664
Subject(s) - genome wide association study , biology , hepatitis b virus , virology , expression quantitative trait loci , genetic association , locus (genetics) , genetics , gene , immunology , virus , genotype , single nucleotide polymorphism
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.