Interpreting variants associated with congenital heart disease with a regulatory map of the human fetal heart

Gene regulation map of the human fetal heart reveals that both rare coding and common noncoding variants associated with CHD converge on valvular interstitial cells (VICs).

• Why it matters: Understanding how genetic variants influence heart development is crucial for deciphering the molecular basis of congenital heart disease and improving targeted therapies.
• What they did: Researchers collected single-cell multiomic data from 734,000 cells across 41 fetal hearts from weeks 6 to 22, constructing gene regulation maps in 90 cardiac cell types and states, including rare populations.
• The result: Findings suggest that variants impact VICs and specific heart structures through enhancers, implicating new genes and cell types in CHD etiology and providing a resource for interpreting genetic variants and developing cell-type specific interventions.