Heart failure & cardiomyopathies
A Common CD36 Variant and the Genetic Landscape of Dilated Cardiomyopathy in Individuals of African Ancestry
Authors' conclusion
In 4 US cohorts, an ancestry-specific CD36 variant contributed more to DCM burden among individuals of African ancestry than established genes for DCM, including TTN truncating variants that are typically considered the most common genetic cause. These findings reshape the known genetic architecture of DCM in individuals of African ancestry and highlight the importance of representation in genomic research.
Study context
- Population
- Participants of African and European ancestry with exome or genome sequence data and dilated cardiomyopathy (DCM) case status from All of Us Research Program, Million Veteran Program, Penn Medicine Biobank and the DCM Precision Medicine Studyindividuals of predominantly African ancestry across 4 cohorts, 1316 had DCM
- Participants
- 82,623 participants
- Comparison
- Contribution of a CD36 nonsense variant to DCM risk vs that of truncating variants in TTN and pathogenic or likely pathogenic variants in other established genes for DCM
- Outcome
- Risk of DCM, prevalence of variant carriers among DCM cases, and population attributable fraction of DCM
Methodological details4 US datasets, exome or genome sequence data
- 4 US datasets
- Exome or genome sequence data
Further findings
| Outcome | CD36 Y325* homozygous | CD36 Y325* heterozygous | TTN truncating variants | Pathogenic or likely pathogenic variants in other high-confidence genes | |
|---|---|---|---|---|---|
| Prevalence of variant carriers among 1316 DCM cases of African ancestry | 2.5% | Not reported in the abstract | 4.3% | 1.2% | CD36 Y325* heterozygous: not reported in the abstract |
- Risk of DCM with TTN truncating variants (African ancestry)
- 8.5 · OR · 95% CI 5.5–13.0
- Prevalence of variant carriers among 1316 DCM cases of African ancestry: of the 1316 DCM cases
Risk of DCM by CD36 Y325* genotype
| Population | OR (95% CI) | |
|---|---|---|
| CD36 Y325* homozygous | 4.8 (3.1-7.3) | |
| CD36 Y325* heterozygous | 1.4 (1.2-1.7) | |
| 0.10.31310Odds ratio (log scale) |
- Comparator not stated in the abstract
Population attributable fraction of DCM
- CD36 (heterozygous and homozygous carriers)
- 9.0%
- CD36 heterozygous carriers
- 6.2%
- CD36 homozygous carriers
- 2.8%
- TTN truncating variants
- 3.7%
Baseline characteristics (African ancestry)
- Mean age
- 53.4 years (SD, 13.9 years)
- Male
- 47 124
- Had DCM
- 1316
Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.
Original publication
Summarised from the published abstract; every number is checked against it