Journal article

The Human Leukocyte Antigen Locus and Rheumatic Heart Disease Susceptibility in South Asians and Europeans

Kathryn Auckland, Balraj Mittal, Benjamin J Cairns, Naveen Garg, Surendra Kumar, Alexander J Mentzer, Joseph Kado, Mai Ling Perman, Andrew C Steer, Adrian VS Hill, Tom Parks

Scientific Reports | NATURE RESEARCH | Published : 2020

Abstract

Rheumatic heart disease (RHD), an autoinflammatory heart disease, was recently declared a global health priority by the World Health Organization. Here we report a genome-wide association study (GWAS) of RHD susceptibility in 1,163 South Asians (672 cases; 491 controls) recruited in India and Fiji. We analysed directly obtained and imputed genotypes, and followed-up associated loci in 1,459 Europeans (150 cases; 1,309 controls) from the UK Biobank study. We identify a novel susceptibility signal in the class III region of the human leukocyte antigen (HLA) complex in the South Asian dataset that clearly replicates in the Europeans (rs201026476; combined odds ratio 1.81, 95% confidence interva..

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Grants

Awarded by British Heart Foundation


Awarded by Medical Research Council


Awarded by National Institute for Health Research


Awarded by British Heart Foundation Centre of Research Excellence, Oxford


Awarded by Wellcome Trust Fellowship


Awarded by Wellcome Trust Senior Investigator Award


Awarded by European Research Council advanced grant


Awarded by Wellcome Trust


Awarded by Wellcome Trust Core Award


Funding Acknowledgements

We thank the investigators of the Pacific Islands Rheumatic Heart Disease Genetics Network which facilitated the sample collection in Fiji. We also thank the UK Biobank Resource (application number 11537), on which part of this research has been conducted. This work was supported by grants awarded to T.P. from the British Heart Foundation [PG/14/26/30509], the Medical Research Council [G1100449], the British Medical Association [Josephine Lansdell Grant 2018; Josephine Lansdell Grant 2012] and the National Institute for Health Research [ACF-2016-20-001], and to B.J.C. from the British Heart Foundation Centre of Research Excellence, Oxford [RE/13/1/30181]. A.J.M. was supported by a Wellcome Trust Fellowship with reference 106289/Z/14/Z and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). A.V.S.H. is supported by a Wellcome Trust Senior Investigator Award [HCUZZ0] and by a European Research Council advanced grant [294557]. 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 Centre for Human Genetics for generating the genotyping and sequencing data, subsidized by a core award from the Wellcome Trust [090532/Z/09/Z]. Computation used the Oxford Biomedical Research Computing (BMRC) facility, a joint development between the Wellcome Centre for Human Genetics and the Big Data Institute supported by Health Data Research UK and the NIHR Oxford Biomedical Research Centre. Financial support was provided by the Wellcome Trust Core Award Grant Number 203141/Z/16/Z. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.