Rare Genetic Variants Associated With Myocardial Fibrosis: Multi-Ethnic Study of Atherosclerosis

• DOI: 10.3389/fcvm.2022.804788
• Publication Date: 2022-02-21T10:59:57Z
• Authors: Mahsima Shabani; Diptavo Dutta; Bharath Ambale-Ve...; Wendy S. Post; Kent D. Taylor; Stephen S. Rich; Colin O. Wu; Naveen L. Pereira; Sanjiv J. Shah; Nilanjan Chatterjee; Jerome I. Rotter; Dan E. Arking; Joao A. C. Lima
• Keywords: Myocardial fibrosis

Background Rare pathogenic variants in cardiomyopathy (CM) genes can predispose to cardiac remodeling or fibrosis. We studied the carrier status for such adults without clinical cardiovascular disease (CVD) whom MRI (CMR)-derived measures of myocardial fibrosis were obtained Multi-Ethnic Study Atherosclerosis (MESA). Objectives To identify CM-associated and assess their relative prevalence participants with extensive by CMR. Methods MESA whole-genome sequencing data was evaluated capture ( n = 82). Coding a frequency <0.1% gnomAD 1,000 Genomes Project databases damaging/deleterious effects based on in-silico scoring tools assessed ClinVar database ACMG curation guidelines evidence pathogenicity. Cases high defined as highest quartile extracellular volume (ECV) native T1 time T1-mapping CMR controls remainder participants. Results A total 1,135 had available genetic phenotypic free CVD at identified 6,349 rare overall population, which six pathogenic/likely (P/LP) present phenotyped subpopulation. The harboring P/LP case group MYH7, CRYAB , SCN5A . cases higher than (5 420 [1.1%] vs. 1 715 [0.1%], p 0.03). two MYBPC3 Variants Unknown Significance (VUS)s borderline pathogenicity group. left ventricle (LV) volume, mass, ejection fraction (EF), longitudinal circumferential strain not different compared cohort. Conclusions observed potentially CM associated significant quantified No structural functional differences found between variants.