An exciting discovery sheds light on the genetics of Rheumatic Heart Disease (RHD) in Black Africans, through the collaboration of eight African countries, and international partnerships including genetic data analyzed in a laboratory located at PHRI.

Results were published in JAMA Cardiology today, as “Association of novel locus with rheumatic heart disease in black African individuals: findings from the RHDGen study.

L to R: Mayosi, Zühlke and Engel

Led by the University of Cape Town (UCT), the genome-wide association study discovered a ‘locus’ (genetic location on a chromosome) associated with RHD susceptibility in Black Africans among the 4809 individual participants and 348 participants in families in Kenya, Mozambique, Namibia, Nigeria, South Africa, Sudan, Uganda, and Zambia.

One of the largest African genetic studies of its kind ever conducted, the Genetics of Rheumatic Heart Disease (RHDGen) was inspired by the late Bongani Mayosi and conceived in partnership with colleagues at the universities of Manchester and Newcastle in the UK, and McMaster University and PHRI.

“The RHDGen study provides a striking example of continental collaboration and international partnership tackling a much-neglected disease, while contributing to building research capacity on the African continent for the next big project,” says Liesl Zühlke, UCT acting dean (research), pediatric cardiologist, and co-principal investigator of this study with UCT epidemiologist Mark Engel.

Tafadzwa Machipisa

RHD is a leading cause of cardiac surgery in sub-Saharan African and a major cause of morbidity and mortality, yet the disease is poorly understood and under-studied.

The DNA of study participants (ethnically matched cases and controls) was extracted at the cardiovascular genetics laboratory at the Hatter Institute for Cardiovascular Research in Africa and the Cape Heart Institute at UCT.

DNA samples were then genotyped at the genetic and molecular epidemiology laboratory in Hamilton, Canada using powerful technology that examines up to millions of genotypes for a single individual at once, and accessing the genotyping imputation and phasing service provided by the Wellcome Sanger Institute.

Machipisa, Mayosi, Muhamed, Paré

McMaster University, along with the universities of Manchester and Newcastle in the UK, provided support for training of young African scientists, including Tafadzwa Machipisa, first author on the JAMA Cardiology publication.

A final year UCT PhD student, Machipisa led the complex genetic analysis under the guidance of Guillaume Paré, director of the lab where the DNA for the RHDGen study was analyzed, and a joint senior author on the paper.

(Two of the paper’s coauthors are Michael Chong, a bioinformatician in training at Paré’s lab, and UCT student Babu Muhamed, who formerly studied under Paré in Canada.)

Machipisa notes that “our findings may provide insight as to why RHD is even more common in Black Africans, than in previously studied populations,” says Machipisa.

“RHDGen results will further allow inter-study analyses to get the bigger picture on a global population scale, to find global solutions to the RHD epidemic.”

Paré notes that “the next step is to further investigate our top candidate genes, using functional analyses and explore biomarker-based methods to understand the process of disease development.”

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