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We performed a two-stage genome-wide association study (GWAS) of antibody titer in 3614 hepatitis B vaccine recipients from Indonesia's Riau Archipelago, leading to the identification of at least three independent signals within the human leukocyte antigen (HLA) complex. These appear to implicate HLA-DR [rs3135363;  P = 6.53 × 10 −22 ; odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.35–1.74]; HLA-DP, previously associated with the risk of chronic hepatitis B infection (rs9277535;  P = 2.91 × 10 −12 ; OR = 0.72, 95% CI = 0.63–0.81); and a gene rich HLA Class III interval (rs9267665;  P  = 1.24 × 10 −17 ; OR = 2.05, CI = 1.64–2.57). The substantial overlap of these variants and those identified by GWAS of chronic hepatitis B infection confirms vaccine response as a model for infection, while suggesting that the vaccine is least effective in those most at risk of lifelong infection, following exposure to the virus.

human molecular genetics

A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region