Prevalence of deleterious variants in cardiomyopathy genes in early-onset atrial fibrillation

Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke, heart failure, and death. Recent studies suggest that early-onset AF increases the risk of developing heart failure and dilated cardiomyopathy. This study aimed to identify genetic variants in a large set of 34 cardiomyopathy genes among early-onset AF individuals. We conducted targeted sequencing of cardiomyopathy-associated genes in 478 individuals from a Danish cohort with early AF onset. Additionally, we analyzed whole exome sequencing data from 375,869 individuals from the UK Biobank, including 29,267 individuals with AF. Of the Danish individuals with early-onset AF, 8.8% carried pathogenic or likely pathogenic (P/LP) variants in cardiomyopathy-associated genes. The prevalence of rare P/LP variants in the UK Biobank analysis ranged from 3.85% in the group with early AF onset to 1.03% in the group without AF diagnosis. Results were largely consistent when excluding individuals with no prior cardiomyopathy or heart failure diagnosis. This suggests that genetic testing for cardiomyopathy could be relevant in selected individuals with early AF diagnosis.