Biology Faculty Articles
Document Type
Article
Publication Date
1-13-2021
Publication Title
BMC Medical Genomics
Keywords
HBV infection, disease progression, GWAS, Host genetic factors, SNPs
ISSN
1755-8794
Abstract
Background: Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes.
Results: In order to discover new susceptibility genes for HBV-related outcomes, we conducted a genome-wide association study in 1031 Chinese participants, including 275 HBV clearance subjects, 92 asymptomatic persistence infection carriers (ASPI), 93 chronic hepatitis B patients (CHB), 188 HBV-related decompensated cirrhosis patients (DC), 214 HBV-related hepatocellular carcinoma patients (HCC) and 169 healthy controls (HC). In the case-control study, we observed novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57×10-6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62×10-6; SNP: rs4661093, Gene: ETV3, P = 2.26×10-6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85×10-6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Interestingly, underlying the evolutionary study of HBV-related genes in public database, we found that the derived allele of two HBV clearance related locus, rs3077 and rs9277542, are under strong selection in European population.
Conclusions: In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Moreover, we identified two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
NSUWorks Citation
Zeng, Zheng; Liu Hankui; Xu Huifang; Lu Haiying; Yu Yanyan; Xu Xiaoyuan; Yu Min; Zhang Tao; Tian Xiulan; Xi Hongli; Guan Liping; Zhang Jianguo; and Stephen James O'Brien. 2021. "Genome-wide Association Study Identifies New Loci Associated With Risk Of HBV Infection And Disease Progression." BMC Medical Genomics , (). doi:10.21203/rs.3.rs-143403/v1.
ORCID ID
0000-0001-7353-8301
ResearcherID
N-1726-2015
DOI
10.21203/rs.3.rs-143403/v1
Comments
This study was supported by the National Natural Science Foundation of China (No. 61972007, No. 30671855), the International Science & Technology Cooperation Program of China (No. 2014DFR31200), Federal funds from the National Cancer Institute, National Institutes of Health, USA (No. N01-CO-12400), Shenzhen Municipal of Government of China (JCYJ20170412153248372, JCYJ20180507183615145).