Design: Multicohort genetic association study
Population: 82,623 people of African ancestry in 4 US cohorts; 1,316 with dilated cardiomyopathy
Primary outcome: Risk of dilated cardiomyopathy and population attributable fraction
Effect: Homozygous OR 4.8 (3.1–7.3); PAF 9.0% vs 3.7% for titin truncating variants

A JAMA genetic association study combined four US cohorts with sequencing data, including 82,623 people of predominantly African ancestry, of whom 1,316 had dilated cardiomyopathy.

Homozygotes for the CD36 Y325* nonsense variant had an OR of 4.8 for dilated cardiomyopathy, and heterozygotes 1.4. Titin truncating variants carried a higher individual risk (OR 8.5) but are rarer. Because the CD36 variant is common, its population attributable fraction was 9.0%, against 3.7% for titin truncating variants.

Standard cardiomyopathy gene panels are built largely on European-ancestry data and may not include CD36. For patients of African ancestry with unexplained dilated cardiomyopathy, a negative panel may therefore miss the most common genetic contributor.

This is association data and does not yet tell us whether carriers need screening or different treatment. It is a reason to check what a panel covers, not to change management.

Check whether your cardiomyopathy gene panel includes CD36 when testing patients of African ancestry
Do not treat a negative standard panel as excluding a genetic cause in these patients
Take a three-generation family history in every patient with unexplained dilated cardiomyopathy
Offer family echocardiographic screening as current guidance advises, whatever the genetic result

Why it matters

Gene panels built on European data can miss the commonest genetic contributor in other populations.

The statistics, in plain English

The population attributable fraction estimates how much disease would disappear if the variant's effect were removed. A modest per-person risk (OR 1.4 in heterozygotes) can still account for more cases than a rare, high-risk variant when many people carry it.