Heart failure & cardiomyopathies
Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry
Main finding · Clinically actionable variantsResult — go to the resultOdds ratio 0.25 95% CI 0.17–0.37Authors' 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)
Methodological detailsmulticentre, 25 US advanced HF programs
- Multicentre
- 25 US advanced HF programs
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 patientAfrican ancestry vs European ancestry · clinically actionable variants in TTN | −0.09 (−0.14 to −0.05) | |
| Number of variants per patientAfrican ancestry vs European ancestry | −0.06 (−0.11 to −0.02) | |
| Number of variants per patientAfrican ancestry vs European ancestry · pathogenic/likely pathogenic/VUS variants | −0.07 (−0.22 to 0.09) | |
| Number of variants per patientAfrican 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.
Summarised from the published abstract; every number is checked against it