Rheumatic Heart Disease Risk Genetically Linked to African Patients

Tafadzwa Machipisa, MPhil

A breakthrough study from South Africa linked specific genetic features in Black African individuals to an increased susceptibility to rheumatic heart disease (RHD), with an estimated Polygenic heritability of 0.49.

The findings come 3 years after the World Health Organization (WHO) categorized RHD as a global health priority. The disease is associated with nearly 10.5 billion disability-adjusted-life-years and linked to 300,000 premature deaths.

Despite global advancements in combatting the disease, some low- and middle-income countries have continued to grapple with rheumatic heart disease. Sub-Saharan Africa, home to 17% of the world’s total population, recorded 23% of all global cases of RHD as recently as 2017.

Additionally, rheumatic heart disease remains the most prevalent form of cardiovascular disease in Black African women and children, with prevalence most frequently occurring between ages 24 and 45.

While not always the case, the disease had been linked to rheumatic fever. Nearly 60% of cases of rheumatic fever eventually progress to RHD.

The research team, lead by Tafadzwa Machipisa, MPhil, gained a better understanding of the hereditary nature of rheumatic disease by studying a variety of Black African individuals. Though small in size, the study included participants from 8 countries including Kenya, Mozambique, Namibia, Nigeria, South Africa, Sudan, Uganda, and Zambia.

The study consisted of 4809 participants (2546 cases plus 2261 controls), all of whom participated in genome-wide association studies (GWAS). Prior GWAS recorded RHD susceptibility in 4 different populations and acted as an inspiration for the team’s study.

The GWAS conducted for the study were used to measure risk scores in Black African participants and determine specific loci.

“Understanding genetic susceptibility will help devise better prevention, control, and interventions,” the team wrote.

Additionally, the team extracted DNA from participants at the genetics laboratory at the Hatter for Cardiovascular Research in Africa and the Cape Heart Institute of the University of Cape Town, to be genotyped.

Despite limitations such as a small size and the lack of cohort studies on the subject, the investigators provided loci and new pathways towards determining RHD susceptibility.

“To our knowledge, we provided the first chip-based heritability estimates for RHD in African samples,” the team wrote. “Our estimates of 0.35 in admixed African individuals and 0.49 in Black African individuals support an important association of host genetics with RHD susceptibility.”

The novel candidacy susceptibility locus found in the study was specific to Black African individuals. The team replicated 75 previous loci during the study, but no significant advancements were made in locating additional genetic associations. In some cases certain loci could not be replicated.

The investigators recommended further study and replication of GWAS, specifically on Black African individuals. Despite limitations, the study provided a path forward in further determining risk in specific groups and combatting rheumatic heart disease in low-to-middle income countries.

“Our results also support a high heritability for RHD in African individuals, providing a basis for the familial aggregation of RHD cases beyond a shared environment,” investigators concluded. “As with other polygenic traits, large sample sizes will be necessary to uncover the numerous variants with smaller effect sizes underlying RHD risk.”

The study, “Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals” was published online in JAMA Cardiology.