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Rheumatic Heart Disease Susceptibility in Black African Individuals
Quick Takes
- This genome-wide association study (GWAS) has identified a rheumatic heart disease (RHD) risk locus specific to Black African individuals.
- A polygenic risk score was found to be higher among RHD patients as compared with their unaffected parents.
Study Questions:
What genetic loci are associated with increased rheumatic heart disease (RHD) susceptibility in Black African individuals?
Methods:
This multicenter, case-control, genome-wide association study (GWAS) evaluated over 7 million single-nucleotide variations among 4,809 participants (2,548 cases and 2,261 controls) and 116 independent trio families from eight African countries. All participants were screened for RHD with echocardiography.
Results:
Approximately two-thirds (66%) of patients self-identified as Black, 22% as mixed race, and 12% as other (North African, Arab, Asian, or European ancestry). RHD patients were disproportionately female (75% of cases, 61% of controls, p < 0.001). Atrial fibrillation was present in 23% of cases and 0.1% of controls (p < 0.001). The most common type of valvular dysfunction among RHD patients was mitral regurgitation (60%), followed by tricuspid regurgitation (54%), aortic regurgitation (38%), and mitral stenosis (34%).
The GWAS identified a single RHD risk locus, 11q24.1, that reached genome-wide significance specifically in Black African individuals (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.48-1.82; p = 4.36 x 10-8) and not in other racial groups. A previously reported association in Pacific Islander individuals, rs1186409 (immunoglobulin heavy chain locus), was also identified in the meta-analysis of Black and mixed-race individuals (OR, 1.16; 95% CI, 1.06-1.27; p = 0.001). A polygenic risk score comprising 195 putative risk variants was found to be higher among probands as compared with their unaffected parents.
Conclusions:
A RHD risk locus specific to Black African individuals has been identified. Analysis of families supports the previous observation that RHD susceptibility is polygenic.
Perspective:
RHD affects approximately 40 million people worldwide and causes nearly 300,000 deaths annually, disproportionately impacting patients in low- and middle-income countries. RHD is an acquired condition that is largely preventable with appropriate antibiotic treatment for streptococcal infections, and it is often under-recognized in low-resource settings. Global improvements in access to care, ranging from primary prevention to cardiac surgery, are needed to reduce the burden of RHD.
Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Cardiovascular Care Team, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Valvular Heart Disease, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and VHD, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound, Mitral Regurgitation
Keywords: African Americans, African Continental Ancestry Group, Aortic Valve Insufficiency, Atrial Fibrillation, Cardiac Surgical Procedures, Developing Countries, Echocardiography, Genetic Loci, Genome-Wide Association Study, Heart Valve Diseases, Mitral Valve Insufficiency, Mitral Valve Stenosis, Primary Prevention, Rheumatic Heart Disease, Risk Factors, Tricuspid Valve Insufficiency
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