Polygenic scores for hypertrophic and dilated cardiomyopathies independently and oppositely modified disease risk and penetrance of pathogenic variants, supporting bidirectional genetic influences on Cardiomyopathy.

Question How is risk of hypertrophic and dilated cardiomyopathy modified by polygenic background?

Findings In this cross-sectional study including 49 434 individuals in the Penn Medicine BioBank, polygenic scores for hypertrophic and dilated cardiomyopathies were associated with clinical and echocardiographic measures relevant to both diseases and inversely modified the penetrance of pathogenic variants.

Meaning The findings indicate that polygenic background exists on an overlapping, opposing spectrum and may contribute to hypertrophic and dilated cardiomyopathy susceptibility.