Shared additive- and variance-associated genetic architecture of cardiac structure and function

In up to 77,271 UK Biobank participants, 96% of multivariate fine-mapped genetic signals for 22 cardiac MRI phenotypes show effects across multiple heart chambers, with 748 additive locus-trait associations.

• Why it matters: Cardiac remodeling drives cardiomyopathy and heart failure, but it is unclear how widely genetic effects are shared across chambers and whether genetic influences on phenotypic variability extend beyond additive effects.
• What they did: The study analyzed 22 cardiac magnetic resonance phenotypes using additive mapping (748 locus-trait associations across 239 regions) and multivariate fine-mapping, then applied variance mapping (19 associations, 13 without nearby additive signals).
• The result: Fine-mapped sharing formed three robust communities linked to atrial function, chamber remodeling, and ventricular systolic function, and variance loci plus polygenic effects generalized to Penn Medicine echocardiographic phenotypes and outcomes.

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