title: A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region.
abstract: 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.
authors.affiliation: 1Human Genetics, Genome Institute of Singapore, Singapore.
authors.forename: Eileen
authors.initials: E
authors.lastname: Png
authors.forename: Anbupalam
authors.initials: A
authors.lastname: Thalamuthu
authors.forename: Rick T H
authors.initials: RT
authors.lastname: Ong
authors.forename: Harm
authors.initials: H
authors.lastname: Snippe
authors.forename: Greet J
authors.initials: GJ
authors.lastname: Boland
authors.forename: Mark
authors.initials: M
authors.lastname: Seielstad
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006508:Hepatitis Antibodies / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D007214:Indonesia; D020641:Polymorphism, Single Nucleotide
chemical_list: D006680:HLA Antigens; D006508:Hepatitis Antibodies; D017325:Hepatitis B Vaccines