| Title: |
High prevalence of deleterious variants in cardiomyopathy genes in patients with early onset atrial fibrillation |
| Authors: |
Vad, O B; Ahlberg, G; Paludan-Muller, C; Refsgaard, L; Sajadieh, A; Haunsoe, S; Bundgaard, H; Svendsen, J H; Olesen, M S |
| Source: |
European Heart Journal ; volume 43, issue Supplement_2 ; ISSN 0195-668X 1522-9645 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2022 |
| Description: |
Background Atrial Fibrillation (AF) is a common cardiac arrhythmia associated with increased morbidity and mortality. AF has a significant heritable component and genome-wide association studies have associated numerous loci in the human genome with AF. The arrhythmia is relatively rare in younger individuals, but studies have shown that individuals with early-onset AF may harbour a considerable burden of pathogenic genetic variants. In recent years, the concept of atrial cardiomyopathy has emerged as a mechanism involved in AF pathogenesis. Genes well-known to be related to ventricular structure, including cardiomyopathies have now also been associated with AF. Purpose Using targeted genetic sequencing, this study aimed to elucidate the role of deleterious genetic variants in cardiomyopathy genes in early-onset AF, and provide new insights into AF pathogenesis. Methods We performed targeted genetic sequencing of 445 Danish individuals with onset of AF before age 40 years and no other cardiovascular co-morbidities, and of 387 controls with no history of AF. Based on guidelines for genetic testing for clinical use, we focused on 30 genes with well-established associations with dilated cardiomyopathy, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. We examined the prevalence of loss-of-function variants (defined as variants leading to premature stop-codon, frameshift or splice-site variants), as these are most likely to be disease-causing. We filtered for rare variants using a minor allele frequency |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/eurheartj/ehac544.2877 |
| Availability: |
https://doi.org/10.1093/eurheartj/ehac544.2877; https://academic.oup.com/eurheartj/article-pdf/43/Supplement_2/ehac544.2877/46365475/ehac544.2877.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.31A6FBAF |
| Database: |
BASE |