Genome-wide association study identifies new loci associated with risk of HBV infection and disease progression

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. Methods Collected samples from different outcomes infection performed genotyping by Affymetrix 500 k SNP Array. GCTA tool, PLINK, Bonferroni method were applied for analysis disease progression. ANOVA was used to evaluate significance association between biomarkers genotypes healthy controls. PoMo, F ST, Vcftools Rehh package building racial tree population analysis. ST statistics accesses 0.15 as a threshold detect signature selection. Results There are 1031 participants passed quality control 1104 participants, including 275 92 asymptomatic persistence (ASPI), 93 B (CHB), 188 decompensated cirrhosis (DC), 214 carcinoma (HCC) 169 controls (HC). In case–control study, one novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2 , P = 1.57 × 10 ?6 ) HCC rs2833856, EVA1C 1.62 ; SNP: rs4661093, ETV3 2.26 ). trend study across progressive stages post infection, rs1537862, LACE1 1.85 ), three MHC loci ( HLA-DRB1, HLA-DPB1, HLA-DPA2 significant increased risk ASPI CHB. Underlying evolutionary public database, derived allele two clearance related loci, rs3077 rs9277542, under strong selection European population. Conclusions this we several candidate individual infectious outcomes, stages, enzymes. Two SNPs that show selective HLA-DPA1 HLA-DPB1 non-East Asian (European, American, South Asian) versus East Asian, indicating contribute ethnic disparities infection. Taken together, findings provided new insight into