Genetic testing in monogenic early-onset atrial fibrillation

Area of Science:

• Cardiovascular Genetics
• Genomic Medicine
• Electrophysiology

Background:

• A significant portion of atrial fibrillation (AF) cases lack identifiable acquired risk factors.
• Current guidelines for genetic testing in AF are limited.
• Understanding the genetic basis of early-onset AF is crucial for personalized medicine.

Purpose of the Study:

• To determine the prevalence of pathogenic variants in established AF genes within a well-characterized early-onset AF cohort.
• To assess the diagnostic yield of whole exome sequencing for monogenic causes of AF.
• To explore the clinical utility of genetic findings in AF management.

Main Methods:

• Whole exome sequencing was performed on 200 patients with early-onset AF (≤60 years) and no acquired risk factors.
• Variants were filtered and classified using ACMG/AMP guidelines.
• Patients were recruited from St. Paul's Hospital and London Health Sciences Centre.

Main Results:

• The study included 200 AF patients, with a mean age of onset at 43.6 years; 83.5% were male and 29.0% had a family history.
• A diagnostic yield of 3.0% was observed for likely pathogenic or pathogenic variants in AF-associated genes.
• 94 individuals presented with very early-onset AF (≤45 years).

Conclusions:

• Whole exome sequencing revealed a 3.0% diagnostic yield for monogenic causes of AF in this cohort.
• Findings suggest potential clinical utility for genetic screening and tailored treatment in AF patients with identified monogenic defects.
• Further research is needed to identify additional genetic determinants, including polygenic factors, for AF patients without a clear genetic explanation.