Host genetic variants near the PAX5 gene locus associate with susceptibility to invasive group A streptococcal disease

We undertook a genome-wide association study of susceptibility to invasive group A streptococcal (GAS) disease combining data from distinct clinical manifestations and ancestral populations. Amongst other signals, we identified a susceptibility locus located 18kb from PAX5 , an essential B-cell gene, which conferred a nearly two-fold increased risk of disease (rs1176842, odds ratio 1.8, 95% confidence intervals 1.5-2.3, P=3.2×10 −7 ). While further studies are needed, this locus could plausibly explain some inter-individual differences in antibody-mediated immunity to GAS, perhaps providing insight into the effects of intravenous immunoglobulin in streptococcal toxic shock.