title: Genome-wide association study identifies SNPs in the MHC class II loci that are associated with self-reported history of whooping cough.
abstract: Whooping cough is currently seeing resurgence in countries despite high vaccine coverage. There is considerable variation in subject-specific response to infection and vaccine efficacy, but little is known about the role of human genetics. 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 the MHC region and carried out gene-based and gene-set tests of association and estimated the amount of additive genetic variation explained by common SNPs. We observed a novel association at SNPs in the MHC class 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. The majority 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.
authors.affiliation: School of Social and Community Medicine and.
authors.forename: George
authors.initials: G
authors.lastname: McMahon
authors.affiliation: School of Social and Community Medicine and MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.affiliation: School of Social and Community Medicine and MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: George
authors.initials: G
authors.lastname: Davey-Smith
authors.affiliation: School of Social and Community Medicine and MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK n.j.timpson@bristol.ac.uk.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D057566:Self Report; D006113:United Kingdom; D014917:Whooping Cough / Q000453:epidemiology / Q000235:genetics*