A genome-wide association study with DNA pooling identifies the variant rs11866328 in the GRIN2A gene that affects disease progression of chronic HBV infection.

Host genetics play a vital role in determining clinical outcomes of hepatitis B virus (HBV) infection. To identify novel susceptibility loci to HBV progression, we carried out a genome-wide association study with DNA pooling. This study assessed the relationship between 8 highly-ranked SNPs selected from our DNA pool and disease progression of HBV infection in two independent case-control studies. The first population included 628 asymptomatic HBV carriers (AsC) and 1729 progressed HBV carriers recruited from Hubei Province in south China. The second population was composed of 226 AsC and 215 progressed HBV carriers recruited from Shandong Province in north China. Of the 8 SNPs, variant rs11866328 (G/T), located in the glutamate receptor ionotropic N-methyl D-aspartate 2A (GRIN2A) gene, was replicated and had significant associations with disease progression of HBV infection in the DNA pooling stage both in the Hubei (OR 1.65; 95% CI 1.34,2.02; p=1.96 × 10(-6); additive model), and in the Shandong (OR 1.73; 95% CI 1.14,2.65; p=1.00×10(-2); additive model) population. Polymorphism rs11866328 in the GRIN2A gene might be a genetic variant underlying the susceptibility of HBV carriers to disease progression.