Genomics-First Evaluation of Heart Disease Associated With Titin-Truncating Variants.

ABSTRACT:

Background

Truncating variants in the Titin gene (TTNtvs) are common in individuals with idiopathic dilated cardiomyopathy (DCM). However, a comprehensive genomics-first evaluation of the impact of TTNtvs in different clinical contexts, and the evaluation of modifiers such as genetic ancestry, has not been performed.

Methods

We reviewed whole exome sequence data for >71 000 individuals (61 040 from the Geisinger MyCode Community Health Initiative (2007 to present) and 10 273 from the PennMedicine BioBank (2013 to present) to identify anyone with TTNtvs. We further selected individuals with TTNtvs in exons highly expressed in the heart (proportion spliced in [PSI] >0.9). Using linked electronic health records, we evaluated associations of TTNtvs with diagnoses and quantitativ

SUBMITTER: Haggerty CM 

PROVIDER: S-EPMC6602806 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature