| Title: | "Evidence of Variations in Genetic Prevalence for Loss of Function PKP2 variants between European and African Ancestry Individuals" |
| Journal: | Genetics in Medicine Open |
| Published: | 1 Apr 2026 |
| DOI: | https://doi.org/10.1016/j.gimo.2026.104397 |
Publication 18135
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Abstract
Purpose Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited condition associated with increased risk for ventricular arrhythmias and sudden cardiac death. Prior ARVC studies contained majority European-ancestry individuals; however, limited data have shown an increase in disease-associated variants in African ancestry individuals. This study aimed to assess genotype/phenotype differences by ancestry across several cohorts. Methods We analyzed genomic and health record data from over 660,000 individuals from four population biobanks. We compared the prevalence of predicted pathogenic variants in four ARVC-associated genes across ancestries and the association with ARVC-related traits. Results We observed that individuals with a PKP2 predicted pathogenic variant were two to three times as likely to be of African ancestry than European ancestry in Cohort 1, All of Us, and the UK Biobank. This difference was not seen in Cohort 3. PKP2 predicted pathogenic heterozygotes were more likely to have an ARVC-related trait in the Cohort 1 and All of Us cohorts but not in Cohort 3 or UK Biobank. Conclusion While African ancestry individuals are more likely to carry a PKP2 predicted pathogenic variant, only European ancestry heterozygotes in Cohort 1 and All of Us had increased odds of an ARVC-related trait, suggesting reduced penetrance or clinical under-recognition of disease in African ancestry individuals.</p>
15 Authors
- Alexandra Winters
- Renae Judy
- Choudhary Anwar A. Chahal
- Ghaith Sharaf Dabbagh
- Ravi A. Shah
- Scott Damrauer
- Melissa A. Kelly
- Cynthia A. James
- Crystal Tichnell
- Brittney Murray
- Diane Smelser
- H. Shanker Rao
- David J. Carey
- Christopher Haggerty
- Eric Carruth
1 Application
| Application ID | Title |
|---|---|
| 48286 | Do persons with epilepsy (PWE) have known pathogenic mutations in ion channel or other known sudden cardiac arrest-related genes at a greater frequency than non-epileptics? |
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