Association of Common Ancestry-Enriched Variants With Cardiomyopathy and Arrhythmias - PubMed
2 hours ago
- #health disparities
- #cardiovascular risk
- #genetics
- Individuals of African ancestry are underrepresented in genetic studies, leading to more variants of uncertain significance (VUS) in genetic testing for cardiomyopathies and arrhythmias.
- 82 ancestry-enriched VUS were identified in 18 cardiomyopathy and arrhythmia genes, with enrichment defined as allele frequency ≥2-fold higher in African ancestry compared to European ancestry.
- Four variants showed significant associations with cardiovascular phenotypes in meta-analysis of two biobanks (All of Us and BioVU): PKP2 p.Val558Ile (ventricular arrhythmias/sudden cardiac death), ELAC2 p.Ile396Val (heart failure and atrial arrhythmias), FLNC p.Gly11Ser and PKP2 p.Val842Ile (heart failure).
- Cardiovascular risk factors were linked to earlier onset of heart failure and atrial arrhythmias in variant carriers, and some variants showed increased arrhythmia burden in participants with heart failure.
- PKP2 p.Val558Ile met criteria for likely pathogenic classification, potentially affecting around 24,000 Black adults in the U.S., highlighting clinical implications.