ArticleEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology2021
Enrichment of loss-of-function and copy number variants in ventricular cardiomyopathy genes in 'lone' atrial fibrillation.
Article in Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 26 citations in OpenAlex.
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- Titin-related familial dilated cardiomyopathy: factors associated with disease onset.European heart journal · 2025Observational
- Atrial fibrillation in former world-class rowers: role of environmental and genetic factors.European heart journal · 2025Article
- Lysine 2-hydroxyisobutyrylation of HXK1 alters energy metabolism and KCell communication and signaling : CCS · 2025Article
- Fine tuning contractility: atrial sarcomere function in health and disease.American journal of physiology. Heart and circulatory physiology · 2024Review
- Integrative multi-omics summary-based mendelian randomization identifies key oxidative stress-related genes as therapeutic targets for atrial fibrillation and flutter.Frontiers in genetics · 2024Article
- Genetic testing in monogenic early-onset atrial fibrillation.European journal of human genetics : EJHG · 2023Article
- Genetic Basis of Early Onset Atrial Fibrillation in Patients without Risk Factors.Journal of cardiovascular development and disease · 2023Article
- Explaining the Unexplained: A Practical Approach to Investigating the Cardiac Arrest Survivor.Arrhythmia & electrophysiology review · 2023Review
- Exploring the complex spectrum of dominance and recessiveness in genetic cardiomyopathies.Nature cardiovascular research · 2023Article
- Genetic variants, pathophysiological pathways, and oral anticoagulation in patients with hypertrophic cardiomyopathy and atrial fibrillation.Frontiers in cardiovascular medicine · 2023Review
- A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus.Genetics and molecular biology · 2022Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsAtrial fibrillation (AF) is a complex heritable disease whose genetic underpinnings remain largely unexplained, though recent work has suggested that the arrhythmia may develop secondary to an underlying atrial cardiomyopathy. We sought to evaluate for enrichment of loss-of-function (LOF) and copy number variants (CNVs) in genes implicated in ventricular cardiomyopathy in 'lone' AF. METHODS AND
resultsWhole-exome sequencing was performed in 255 early onset 'lone' AF cases, defined as arrhythmia onset prior to 60 years of age in the absence of known clinical risk factors. Subsequent evaluations were restricted to 195 cases of European genetic ancestry, as defined by principal component analysis, and focused on a pre-defined set of 43 genes previously implicated in ventricular cardiomyopathy. Bioinformatic analysis identified 6 LOF variants (3.1%), including 3 within the TTN gene, among cases in comparison with 4 of 503 (0.80%) controls [odds ratio: 3.96; 95% confidence interval (CI): 1.11-14.2; P = 0.033]. Further, two AF cases possessed a novel heterozygous 8521 base pair TTN deletion, confirmed with Sanger sequencing and breakpoint validation, which was absent from 4958 controls (P = 0.0014). Subsequent cascade screening in two families revealed evidence of co-segregation of a LOF variant with 'lone' AF.
conclusion'Lone' AF cases are enriched in rare LOF variants from cardiomyopathy genes, findings primarily driven by TTN, and a novel TTN deletion, providing additional evidence to implicate atrial cardiomyopathy as an AF genetic sub-phenotype. Our results also highlight that AF may develop in the context of these variants in the absence of a discernable ventricular cardiomyopathy.
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