The RHDGen Network: Genetics of rheumatic heart disease and molecular epidemiology of Streptococcus pyogenes pharyngitis

Principal Investigator:

Scientific Description: 
The proposed activities for the RHDGen Network are:
  • To build a clinical and laboratory network for the phenotyping of patients with rheumatic heart disease (RHD) and controls;
  • To identify genetic variants affecting susceptibility and resistance to RHD;
  • To train a group of scientists and clinicians in genomic studies of multifactorial disease; and
  • To address ethical, legal, and social issues (ELSI) that are relevant to Africa.

The key goals of the network are:

  • To recruit 2,500 patients with echocardiographically-confirmed RHD.
  • To conduct a case-control genome-wide association study by genotyping 5 million single nucleotide polymorphisms in 1,500 RHD cases and 1,500 unrelated controls using micro-array technology, followed by replication in a further 1,000 independent cases and 2,000 family-based controls, and combined analysis of genotype data from all 2,500 cases and 2,500 controls or pseudo-controls to detect rarer alleles or alleles of smaller effect.
  • To train 16 scientists and clinicians in genomics and ELSI at masters, doctoral and postdoctoral levels.

Lay Description:

Rheumatic heart disease (RHD) results from a harmful response of the immune system to a bacterium called Streptococcus pyogenes or Group A Streptococcus (GAS). Although the development of RHD can be prevented by the treatment of GAS infection with penicillin, this has not been successful in poor countries of Africa. We plan to read the genome of 2,500 people with RHD and compare with 3,500 people without RHD to identify genetic risk factors. It is likely that genetic studies may identify people at high risk for the development of RHD who may be prioritised for preventive treatment and vaccination.