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Cited by 23Atrial Fibrillation Management and OutcomesCardiac electrophysiology and arrhythmiasGenomics and Rare Diseases

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Genetic testing in monogenic early-onset atrial fibrillation

Open access
Chalazan, Brandon, Freeth, Emma, Mohajeri, Arezoo, Ramanathan, Krishnan, Bennett, Matthew, Walia, Jagdeep, Halperin, Laura, Roston, Thomas, Lazarte, Julieta, Hegele, Robert A., Lehman, Anna, Laksman, Zachary·2023·European Journal of Human Genetics
DOI 10.1038/s41431-023-01383-zPMC PMC10325969
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Abstract

A substantial proportion of atrial fibrillation (AF) cases cannot be explained by acquired AF risk factors. Limited guidelines exist that support routine genetic testing. We aim to determine the prevalence of likely pathogenic and pathogenic variants from AF genes with robust evidence in a well phenotyped early-onset AF population. We performed whole exome sequencing on 200 early-onset AF patients. Variants from exome sequencing in affected individuals were filtered in a multi-step process, prior to undergoing clinical classification using current ACMG/AMP guidelines. 200 AF individuals were recruited from St. Paul's Hospital and London Health Sciences Centre who were ≤ 60 years of age and without any acquired AF risk factors at the time of AF diagnosis. 94 of these AF individuals had very early-onset AF ( ≤ 45). Mean age of AF onset was 43.6 ± 9.4 years, 167 (83.5%) were male and 58 (29.0%) had a confirmed family history. There was a 3.0% diagnostic yield for identifying a likely pathogenic or pathogenic variant across AF genes with robust gene-to-disease association evidence. This study demonstrates the current diagnostic yield for identifying a monogenic cause for AF in a well-phenotyped early-onset AF cohort. Our findings suggest a potential clinical utility for offering different screening and treatment regimens in AF patients with an underlying monogenic defect. However, further work is needed to dissect the additional monogenic and polygenic determinants for patients without a genetic explanation for their AF despite the presence of specific genetic indicators such as young age of onset and/or positive family history.

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Metadata

Authors
Chalazan, B., Freeth, E., Mohajeri, A., Ramanathan, K., Bennett, M., Walia, J., Halperin, L., Roston, T., Lazarte, J., Hegele, R. A., Lehman, A., & Laksman, Z.
Affiliations
  • University of British Columbia (CA)
  • Western University (CA)
Corresponding author
Laksman, Zachary
ORCID
Venue
European Journal of Human Genetics
Publisher
Springer Science and Business Media LLC
Published
2023-05-22
Volume
31
Issue
7
Pages
769-775
ISSN
  • 1018-4813 (ISSN-L)
  • 1476-5438
DOI
10.1038/s41431-023-01383-z
PMC
PMC10325969
OpenAlex
W4377242189
Cited by
23
References
38
Citations by year
2026: 3 · 2025: 10 · 2024: 9 · 2023: 1
FWCI
4.53
Type
journal article
Language
en
Open access
Licence
Locations
  • European Journal of Human Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Cardiovascular Society
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
atrial fibrillation, early-onset atrial fibrillation, genetic testing, pathogenic variants, diagnostic yield, ACMG/AMP guidelines, familial atrial fibrillation, genetic screening
MeSH terms
Adult, Atrial Fibrillation, Female, Genetic Testing, Humans, Male, Middle Aged, Phenotype, Risk Factors, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide

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CoChat. (2026). Citation check: Genetic testing in monogenic early-onset atrial fibrillation. https://app.cochat.ai/papers/10.1038/s41431-023-01383-z
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Chalazan, B., Freeth, E., Mohajeri, A., Ramanathan, K., Bennett, M., Walia, J., Halperin, L., Roston, T., Lazarte, J., Hegele, R. A., Lehman, A., & Laksman, Z. (2023). Genetic testing in monogenic early-onset atrial fibrillation. European Journal of Human Genetics. https://doi.org/10.1038/s41431-023-01383-z