Genome-wide association study identifies SNPs in the MHC class II loci that are associated with self-reported history of whooping cough

Abstract

Whooping coughis currently seeing resurgence in countries despite highvaccine coverage. There is considerable variation in subjectspecific response to infection and vaccine efficacy, but little is knownabout the role of humangenetics. We carried out a case-control genome-wide association study of adult or parent-reported history of whooping cough in two cohorts from the UK: the ALSPAC cohort and the 1958 British Birth Cohort (815/758 cases and 6341/4308 controls, respectively). We also imputed HLA alleles using dense SNP data in theMHCregion and carried out gene-based and gene-set tests of association and estimated the amount of additive genetic variation explained by commonSNPs. We observed anovel association at SNPs in theMHCclass II region in both cohorts [lead SNP rs9271768 after meta-analysis, odds ratio [95% confidence intervals (CIs)] 1.47 (1.35, 1.6), P-value 1.21E- 18]. Multiple strong associations were also observed at alleles at the HLA class II loci. Themajority of these associations were explained by the lead SNP rs9271768.Gene-based and gene-set tests and estimates of explainable common genetic variation could not establish the presence of additional associations in our sample. Genetic variation at the MHC class II region plays a role in susceptibility to whooping cough. These findings provide additional perspective on mechanisms of whooping cough infection and vaccine efficacy.