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 V S Hill, Tom Parks

Scientific reports 2020 Jun 02

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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.

Citation

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. The Human Leukocyte Antigen Locus and Rheumatic Heart Disease Susceptibility in South Asians and Europeans. Scientific reports. 2020 Jun 02;10(1):9004