Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania.
other · Level V
Where this comes from
- Record sourced from PubMed, PMID 28492228.
- Also identified by DOI 10.1038/ncomms14946 and PMC identifier 5437274.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The indigenous populations of the South Pacific experience a high burden of rheumatic heart disease (RHD). Here we report a genome-wide association study (GWAS) of RHD susceptibility in 2,852 individuals recruited in eight Oceanian countries. Stratifying by ancestry, we analysed genotyped and imputed variants in Melanesians (607 cases and 1,229 controls) before follow-up of suggestive loci in three further ancestral groups: Polynesians, South Asians and Mixed or other populations (totalling 399 cases and 617 controls). We identify a novel susceptibility signal in the immunoglobulin heavy chain (IGH) locus centring on a haplotype of nonsynonymous variants in the IGHV4-61 gene segment corresponding to the IGHV4-61*02 allele. We show each copy of IGHV4-61*02 is associated with a 1.4-fold increase in the risk of RHD (odds ratio 1.43, 95% confidence intervals 1.27-1.61, P=4.1 × 10<sup>-9</sup>). These findings provide new insight into the role of germline variation in the IGH locus in disease susceptibility.
Medical subject headings
- Alleles
- Genetic Predisposition to Disease
- Immunoglobulin Heavy Chains
- Rheumatic Heart Disease