Polygenic Background and Penetrance of Pathogenic Variants in Hypertrophic and Dilated Cardiomyopathies.

ABSTRACT:

Importance

Polygenic background modifies variant penetrance in hypertrophic (HCM) and dilated (DCM) cardiomyopathy, diseases with opposing morphologic characteristics and inversely related genetic pathways. Whether polygenic susceptibility for one disease protects against monogenic risk for the other remains unexplored.

Objective

To characterize if polygenic background bidirectionally modifies pathogenicity of established rare variants associated with HCM and DCM.

Design

Cross-sectional study.

Setting

The Penn Medicine BioBank (PMBB).

Participants

Volunteers enrolled in PMBB with available electronic health record and genotyping data.

Exposures

Normalized polygenic scores (PGS) for HCM and DCM, as well as carrier status of pathogenic variants in e

SUBMITTER: Abramowitz SA 

PROVIDER: S-EPMC12204268 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature