1. The Human Leukocyte Antigen Locus and Rheumatic Heart Disease Susceptibility in South Asians and Europeans.
- Author
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Auckland K, Mittal B, Cairns BJ, Garg N, Kumar S, Mentzer AJ, Kado J, Perman ML, Steer AC, Hill AVS, and Parks T
- Subjects
- Asian People genetics, Case-Control Studies, Fiji, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, India, Polymorphism, Single Nucleotide, White People genetics, HLA Antigens genetics, Rheumatic Heart Disease genetics
- 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.- Published
- 2020
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