Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania

• DOI: 10.1038/ncomms14946
• Publication Date: 2017-05-11T14:54:23Z
• Authors: Tom Parks; Mariana M. Mirabel; Joseph Kado; Kathryn Auckland; Jaroslaw Nowak; Anna Rautanen; Alexander J. Mentzer; Eloi Marijon; Xavier Jouven; Mai Ling Perman; Tuliana Cua; John K. Kauwe; John B. Allen; Henry Taylor; Kathryn J. Robson; Charlotte M. Deane; Andrew C. Steer; Adrian V. S. Hill; ; Lori Allen; Marvin Allen; Corinne Braunstein; Samantha M. Colqu...; Aurélia Jewine; Maureen Ah Kee; Rina Kumar; William John Martin; Reapi Mataika; Marie Nadra; Shahin Nadu; Take Naseri; Baptiste Noël; Nathalie Simon; Brenton Ward
• Keywords: Genome-wide Association Study; Nonsynonymous substitution

Abstract The indigenous populations of the South Pacific experience a high burden rheumatic heart disease (RHD). Here we report genome-wide association study (GWAS) RHD susceptibility in 2,852 individuals recruited eight Oceanian countries. Stratifying by ancestry, analysed genotyped and imputed variants Melanesians (607 cases 1,229 controls) before follow-up suggestive loci three further ancestral groups: Polynesians, Asians Mixed or other (totalling 399 617 controls). We identify novel signal immunoglobulin heavy chain (IGH) locus centring on haplotype nonsynonymous IGHV4-61 gene segment corresponding to *02 allele. show each copy is associated with 1.4-fold increase risk (odds ratio 1.43, 95% confidence intervals 1.27–1.61, P =4.1 × 10 −9 ). These findings provide new insight into role germline variation IGH susceptibility.