Validation in over 11,000 African-ancestry participants from PMBB supports the association; additional imaging cohorts show carriers have impaired heart function before heart failure.

Experimental validation in hiPSC-derived cardiomyocytes showed CD36 knockdown reduced fatty acid uptake, impaired mitochondrial function, and lowered contractile force, linking CD36 loss of function to a cellular DCM phenotype.

Cardiac MRI data from UK Biobank, MESA, and JHS show rs3211938 GG homozygosity associates with subclinical DCM traits, including reduced LVEF and increased LV volumes, indicating impaired function before overt disease.

Conditioning analyses indicate rs3211938 and rs3211916 reflect the same signal, with rs3211938 highlighted as the likely causal variant due to its functional effects and LD.

Phenome-wide analysis links rs3211938 to cardiomyopathy codes, hypertensive heart disease, defibrillator placement, and metabolic traits like higher HDL traits and serum acetone.

Laboratory studies demonstrated that reducing CD36 expression in heart cells diminishes fatty acid uptake and contraction, supporting a mechanistic link to cardiac energetics.

Replication in PMBB confirmed the DCM association (OR ~1.37), and meta-analysis across MVP and PMBB yielded OR ~1.33 with a possible nonlinear dose-response across genotypes.

The authors suggest these findings could lead to including CD36 in clinical genetic testing for cardiomyopathy and spur exploration of therapies targeting cardiac energy metabolism.

The rs3211938 G allele is a loss-of-function nonsense variant (Y325Ter) in CD36, present in about 9% of African ancestry individuals and under 0.1% of European ancestry individuals, and its link to DCM remains after adjusting for various cardiovascular risk factors.

A large, diverse collaboration identified a common CD36 gene variant that substantially increases the risk of dilated cardiomyopathy (DCM) in people of African ancestry, helping explain part of the higher DCM risk observed in Black individuals.

Context includes quotes from senior investigators about MVP’s role in diverse population research and the potential clinical impact of these findings.

A genome-wide study in 1,802 DCM cases and 93,804 controls of African ancestry identified a significant signal on chromosome 7 in the CD36 region, led by intronic rs3211916 (OR 1.34); a neighboring nonsense variant rs3211938 shows stronger functional relevance and is in high LD with rs3211916.