Heart failure & cardiomyopathiesCohort study
Prevalence of Pathogenic Genetic Variants Across Heart Failure Etiologies in an Admixed Population
- whole-genome sequencing data analysis of a heart failure (HF) cohort
- Rare variants in 123 ClinGen-curated cardiovascular genes classified according to ACMG criteria
- Local ancestry inference
Authors' conclusion
These findings replicate a significant diagnostic yield of molecular genetic testing in individuals with dilated cardiomyopathy but extend the relevance of genetic testing beyond traditionally selected HF subgroups. They also underscore the importance of including non-European and admixed populations in cardiovascular genomics to reduce interpretation bias and improve equity in precision medicine.
Study context
- Population
- Unrelated individuals in the GENIUS-HF cohort with reduced ejection fraction or mildly reduced ejection fraction from diverse etiologies in an admixed populationunrelated individuals in the GENIUS-HF cohort
- Participants
- 1,013 individuals
- Exposure
- Idiopathic dilated cardiomyopathy vs ischemic vs Chagasic HF vs hypertensive
Main finding
As reported in the abstract
Overall
6.5%
Observational data: associations, not effects.
Further findings
Pathogenic variant yield by etiology
At least 1 variant of uncertain significance
- Overall
- 77.7%
Only benign/likely benign variants observed
- Overall
- 15.8%
Genes with causal variants
- TTN variants accounted for nearly half of the causal findings, including novel variants
- 13
- Additional causal variants in MYBPC3, FLNC, BAG3, and DSP
Local ancestry and variant of uncertain significance
- Variant of uncertain significance significantly more frequent in regions with African and Native American ancestry
Original publication
Summarised from the published abstract; every number is checked against it