Genetically based atrial fibrillation: Current considerations for diagnosis and management

Anthony V. Pensa, Jayson R. Baman, Megan J. Puckelwartz, Jane E. Wilcox*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Atrial fibrillation (AF) is the most common atrial arrhythmia and is subcategorized into numerous clinical phenotypes. Given its heterogeneity, investigations into the genetic mechanisms underlying AF have been pursued in recent decades, with predominant analyses focusing on early onset or lone AF. Linkage analyses, genome-wide association studies (GWAS), and single gene analyses have led to the identification of rare and common genetic variants associated with AF risk. Significant overlap with genetic variants implicated in dilated cardiomyopathy syndromes, including truncating variants of the sarcomere protein titin, have been identified through these analyses, in addition to other genes associated with cardiac structure and function. Despite this, widespread utilization of genetic testing in AF remains hindered by the unclear impact of genetic risk identification on clinical outcomes and the high prevalence of variants of unknown significance (VUS). However, genetic testing is a reasonable option for patients with early onset AF and in those with significant family history of arrhythmia. While many knowledge gaps remain, emerging data support genotyping to inform selection of AF therapeutics. In this review, we highlight the current understanding of the complex genetic basis of AF and explore the overlap of AF with inherited cardiomyopathy syndromes. We propose a set of criteria for clinical genetic testing in AF patients and outline future steps for the integration of genetics into AF care.

Original languageEnglish (US)
Pages (from-to)1944-1953
Number of pages10
JournalJournal of cardiovascular electrophysiology
Issue number8
StatePublished - Aug 2022


  • atrial fibrillation
  • catheter ablation
  • dilated cardiomyopathy
  • genetic testing
  • genome-wide association study
  • polygenic risk score

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


Dive into the research topics of 'Genetically based atrial fibrillation: Current considerations for diagnosis and management'. Together they form a unique fingerprint.

Cite this