Heart failure & cardiomyopathiesCross-sectional study
Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry
- Cross-sectional study
- multicentre
- 25 US advanced HF programs
Authors' conclusion
Patients of African ancestry with DCM were less likely to have clinically actionable variants in DCM genes than those of European ancestry due to differences in genetic architecture and a lack of representation of African ancestry in clinical data sets.
Study context
- Population
- Patients with dilated cardiomyopathy (DCM) self-identified as non-Hispanic Black, Hispanic or non-Hispanic White, 25 US advanced HF programs, 2016–2020
- Participants
- 505 / 667 / 26
- Exposure
- African vs European genomic ancestry
- African ancestryn = 505
- European ancestryn = 667reference
- Native American ancestryn = 26
- Outcome
- Variants in 36 DCM genes classified as pathogenic/likely pathogenic/uncertain significance and clinically actionable (pathogenic/likely pathogenic)
Main finding
Clinically actionable variants
Odds ratio
0.25
95% CI 0.17–0.37
By group
African ancestry vs European ancestry
OR 0.25 (95% CI 0.17–0.37)
As reported in the abstract
Observational data: associations, not effects.
Further findings
| Outcome | difference (95% CI) | |
|---|---|---|
| Number of variants per patient — African ancestry vs European ancestry · clinically actionable variants in TTN | −0.09 (−0.14 to −0.05) | |
| Number of variants per patient — African ancestry vs European ancestry | −0.06 (−0.11 to −0.02) | |
| Number of variants per patient — African ancestry vs European ancestry · pathogenic/likely pathogenic/VUS variants | −0.07 (−0.22 to 0.09) | |
| Number of variants per patient — African ancestry vs European ancestry · non-TTN non-predicted loss-of-function VUS, mostly missense | 0.15 (0.00–0.30) | |
| −0.4−0.200.20.4Difference (linear scale) |
- Number of variants per patient: clinically actionable variants in other predicted loss-of-function genes
Published case-based evidence of pathogenicity
- Less available for variants found only in African ancestry patients
- P < 0.001
Original publication
Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry. JAMA. Published 1 August 2023. doi:10.1001/jama.2023.11970
Summarised from the published abstract; every number is checked against it