The genetic architecture of Plakophilin 2 cardiomyopathy.

ABSTRACT:

Purpose

The genetic architecture of Plakophilin 2 (PKP2) cardiomyopathy can inform our understanding of its variant pathogenicity and protein function.

Methods

We assess the gene-wide and regional association of truncating and missense variants in PKP2 with arrhythmogenic cardiomyopathy (ACM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) specifically. A discovery data set compares genetic testing requisitions to gnomAD. Validation is performed in a rigorously phenotyped definite ARVC cohort and non-ACM individuals in the Geisinger MyCode cohort.

Results

The etiologic fraction (EF) of ACM-related diagnoses from truncating variants in PKP2 is significant (0.85 [0.80,0.88], p < 2 × 10^-16), increases for ARVC specifically (EF = 0.96 [0.94,0.97], p

SUBMITTER: Dries AM 

PROVIDER: S-EPMC8486657 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature