Genetically based atrial fibrillation: Current considerations for diagnosis and management

Area of Science:

• Cardiology
• Genetics
• Medical Research

Background:

• Atrial fibrillation (AF) is the most prevalent atrial arrhythmia, presenting diverse clinical phenotypes.
• Genetic investigations into AF have primarily focused on early-onset or lone cases.
• Identifying genetic variants associated with AF risk is crucial due to its heterogeneity.

Purpose of the Study:

• To review the current understanding of the genetic basis of atrial fibrillation.
• To explore the genetic overlap between AF and inherited cardiomyopathy syndromes.
• To propose criteria for genetic testing in AF patients and outline future integration into clinical care.

Main Methods:

• Review of linkage analyses, genome-wide association studies (GWAS), and single gene analyses.
• Analysis of genetic variants associated with AF risk and overlap with cardiomyopathy genes.
• Evaluation of current barriers to genetic testing utilization in AF.

Main Results:

• Numerous rare and common genetic variants linked to AF risk have been identified.
• Significant overlap exists between AF genetic variants and those implicated in dilated cardiomyopathy syndromes, including titin gene variants.
• Challenges in AF genetic testing include unclear clinical outcome impact and a high prevalence of variants of unknown significance (VUS).

Conclusions:

• Genetic testing is a reasonable option for patients with early-onset AF or a significant family history of arrhythmia.
• Emerging data suggest genotyping can inform AF therapeutic selection.
• Further research is needed to address knowledge gaps and integrate genetic insights into AF patient care.