Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals: Findings From the RHDGen Study

Area of Science:

• Genetics
• Cardiovascular Disease Epidemiology
• Genomics

Background:

• Rheumatic heart disease (RHD) is a significant cause of cardiac surgery in Africa, yet its genetic underpinnings are not well understood.
• Identifying genetic factors for RHD can inform strategies for prevention and elimination.
• Previous genetic studies on RHD have primarily focused on non-African populations.

Purpose of the Study:

• To identify common genetic loci associated with susceptibility to Rheumatic Heart Disease (RHD) in individuals of Black African ancestry.
• To investigate the genetic architecture of RHD in a large, diverse African cohort.

Main Methods:

• A multicenter, case-control genome-wide association study (GWAS) involving over 7 million single-nucleotide variations.
• Enrollment of 4809 participants (2548 RHD cases, 2261 controls) and 116 independent trio families from 8 African countries.
• Echocardiographic screening of all participants and analysis of genotyped and imputed data.

Main Results:

• A novel RHD risk locus at 11q24.1 (rs1219406) reached genome-wide significance in Black African individuals.
• Meta-analysis revealed suggestive loci and replicated a known association at the immunoglobulin heavy chain locus (rs11846409).
• Significant heritability (0.49) and polygenic risk score overtransmission indicate a strong genetic component for RHD in this population.

Conclusions:

• A novel genetic susceptibility locus for RHD, specific to Black African populations, has been identified.
• The study confirms a substantial heritable component contributing to RHD susceptibility in African individuals.
• These findings are vital for developing targeted interventions and understanding RHD pathogenesis in Africa.