Oral Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Host genetic susceptibility to rheumatic heart disease (#29)

Kathryn Auckland 1
  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OXFORDSHIRE, United Kingdom

Rheumatic heart disease (RHD) remains a leading cause of cardiovascular morbidity and mortality among children and young adults across much of the developing world. Current understanding of the disease’s pathogenesis is unrefined compounding limited preventative strategies.

We recently completed a genome-wide association study (GWAS) of RHD susceptibility in 2,852 individuals recruited across Oceania and identified a novel susceptibility signal in the immunoglobulin heavy chain (IGH) locus. We found that nonsynonymous IGHV4-61 variants tagged the IGHV4-61*02 allele and demonstrated that each copy of IGHV4-61*02 was associated with a 1.4-fold increase in the risk of RHD at genome-wide significance.

In addition, we have now undertaken a second GWAS in 854 individuals recruited in Lucknow, Northern India. In combining these data with those from 309 individuals of Fijian Indian ancestry, we not only confirm our earlier IGH finding but we further identify a signal at genome-wide significance located in the human leukocyte antigen (HLA) class III region. This appears to comprise two independent signals, the first spanning HLA class I (HLA-B) and the second HLA class II (HLA-DQA1/B1).

Overall, our study provides promising insight into the pathogenesis of this devastating disease and is a stepping-stone towards large-scale collaborative meta-analyses that will facilitate translational therapeutic discovery.