| Title: | The Human Leukocyte Antigen Locus and Rheumatic Heart Disease Susceptibility in South Asians and Europeans |
| Journal: | Scientific Reports |
| Published: | 2 Jun 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32488134/ |
| DOI: | https://doi.org/10.1038/s41598-020-65855-8 |
| URL: | https://www.nature.com/articles/s41598-020-65855-8.pdf |
Publication 5861
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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.</p>
11 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
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