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

Genome-wide association study of susceptibility to rheumatic heart disease in South Asians: Preliminary results (#172)

Kathryn Auckland 1 , Alexander Mentzer 1 , Surendra Kumar 2 , Mansi Bhatt 3 , Joseph Kado 4 , Mai Ling Perman 4 , Andrew Steer 5 , Adrian Hill 1 , Balraj Mittal 2 , Tom Parks 1
  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
  2. Babasaheb Bhimrao Ambedkar University, Lucknow, India
  3. Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
  4. Fiji National University, Suva, Fiji
  5. Murdoch Children’s Research Institute, Melbourne, Victoria, Australia


Rheumatic heart disease (RHD) remains a leading cause of morbidity and premature mortality in developing countries. Recently, large-scale genetic studies have begun to provide much needed insight into the underlying pathogenesis.


We undertook a genome-wide association study of RHD susceptibility in 1163 individuals of Indian ancestry recruited in Fiji (n=309) and Northern India (n=854). Patients with incident or prevalent RHD were recruited as cases, while members of the general population were recruited as controls. We genotyped all individuals at ~250,000 variants using the Illumina HumanCore platform before estimating the genotypes of an additional ~5,000,000 variants by imputation. We used linear mixed models to analyse genotyped and imputed variants before combining association statistics from the two datasets using fixed-effects meta-analysis.


We observed a single signal at genome-wide significance, located in the human leukocyte antigen (HLA) class III region (OR=1.91, P=6.8 x 10-9). Using conditional analyses, we demonstrated this was comprised of two independent signals, the first spanning HLA class I (HLA-B) and the second HLA class II (HLA-DQA1/B1). While the IGHV4-61 signal was apparent, as previously reported in the Fijian Indian data (P=0.006), the signal was essentially absent in the Northern Indian data (P=0.25), leaving only negligible signal in the pooled analysis (OR=1.21, P=0.084).


By combining new data from India with previously reported data from Fiji, we provide the first insight into genetic architecture of RHD in South Asians with a promising finding in the HLA locus. We also highlight the challenge of heterogeneity between populations.