Journal article
Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania
T Parks, MM Mirabel, J Kado, K Auckland, J Nowak, A Rautanen, AJ Mentzer, E Marijon, X Jouven, ML Perman, T Cua, JK Kauwe, JB Allen, H Taylor, KJ Robson, CM Deane, AC Steer, AVS Hil
Nature Communications | NATURE PORTFOLIO | Published : 2017
DOI: 10.1038/ncomms14946
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 correspo..
View full abstractGrants
Awarded by Fédération Française de Cardiologie
Funding Acknowledgements
This research was supported by grants awarded to T.P. from the British Heart Foundation (PG/14/26/30509), the Medical Research Council (G1100449) and the British Medical Association (Josephine Lansdell Grant 2012). In addition, M.M.M. received funding from La Fondation pour la Recherche Medicale (FDM20140630267), la Federation Francaise de Cardiologie (Bourse d'etudes a l'etranger) and la Fondation Lefoulon Delalande (Bourse post-doctorale); J.N. and C.M.D. received funding from the Engineering and Physical Sciences Research Council (EP/G037280/1); A.J.M. holds a Wellcome Trust Clinical Research Training Fellowship (106289/Z/14/Z); A.C.S. holds a Career Development Fellowship from National Health and Medical Research Council of Australia (1127077) and a Future Leader Fellowship from the National Heart Foundation of Australia (101174); and A.V.S.H. holds Senior Investigator awards from the Wellcome Trust (104750/Z/14/Z) and National Institute for Health Research (NF-SI-0514-10158). None of these funders had any role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics for generating the genotyping and sequencing data, subsidized by a core award from the Wellcome Trust (090532/Z/09/Z). We also thank Dr Tara Mills for valuable suggestions regarding the sample collection, Professors Gilean McVean, Jonathan Marchini and Andrew Morris for helpful advice about study design and statistical analysis and Dr Corey Watson for useful discussions concerning the immunoglobulin heavy chain locus. Finally, we thank Professor John Clegg for permission to use the existing Oceanian sample collection and Professors David Weatherall, Don Bowden and their many colleagues for the work involved in establishing that collection.