Introduction
Atrial fibrillation (AF) is the most common clinical arrhythmia. While some rare monogenic or Mendelian forms of AF have identified non-AF manifestations1, the common forms of AF do not. Recent insights into the genetics of common AF suggest that the disease, while manifesting in the atrial myocardium, may also have a somatic “non-AF” phenotype2. Patients with AF often manifest with sinus node dysfunction, heart block, atrial flutter, cardiac thrombi, coronary disease and other atrial arrhythmias. The relationship between these discrete phenotypes is thought to be secondary to overlapping upstream biological risk factors. We sought to investigate the potential presence of a non-AF phenotype of AF through associations with polygenic AF risk.
Since the first identified single nucleotide variant (SNV) predisposing to AF was identified3, a cascade of other variants have been implicated in the heritable contribution to AF. This has allowed the creation of polygenic risk scores which aggregate risk across multiple loci to approximate the risk to an individual. While the clinical utility of such scores remains uncertain, they do offer opportunity to define whether discrete clinical features are associated with specific genetic risk. We sought to determine if more granular clinical features might be associated with a defined polygenic risk to AF.