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 intervals 1.51-2.18, P = 3.48×10-10). Importantly, this signal remains despite conditioning on the lead class I and class II variants (P = 0.00033). These findings suggest the class III region is a key determinant of RHD susceptibility offering important new insight into pathogenesis while partly explaining the inconsistency of earlier reports.
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Authors | Kathryn Auckland, Balraj Mittal, Benjamin J Cairns, Naveen Garg, Surendra Kumar, Alexander J Mentzer, Joseph Kado, Mai Ling Perman, Andrew C Steer, Adrian V S Hill, Tom Parks |
Journal | Scientific reports
(Sci Rep)
Vol. 10
Issue 1
Pg. 9004
(06 02 2020)
ISSN: 2045-2322 [Electronic] England |
PMID | 32488134
(Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Asian People
(genetics)
- Case-Control Studies
- Fiji
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- HLA Antigens
(genetics)
- Humans
- India
- Polymorphism, Single Nucleotide
- Rheumatic Heart Disease
(genetics)
- White People
(genetics)
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