Journal
HUMAN MOLECULAR GENETICS
Volume 20, Issue 19, Pages 3893-3898Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddr302
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Funding
- Agency for Science Technology and Research, Singapore (A*STAR)
- US Defense Advanced Research Projects Agency (DARPA) [N66001-08-C-2014]
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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 x 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 x 10(-12); OR = 0.72, 95% CI = 0.63-0.81); and a gene rich HLA Class III interval (rs9267665; P = 1.24 x 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.
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