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

Sci Rep. 2020 Jun 2;10(1):9004. doi: 10.1038/s41598-020-65855-8.


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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • HLA Antigens