Unbiased characterization of atrial fibrillation phenotypic architecture provides insight to genetic liability and clinically relevant outcomes.

Patient subgroups identified by unsupervised clustering were distinguished by comorbidity burden and associated with risk of clinically important outcomes. Polygenic liability to AF across clusters was greatest in the low comorbidity subgroup. Clinical inflammation, as reflected by measured biomarkers, was lowest in the subgroup with lowest comorbidities. However, there were no differences in genetically predicted levels of inflammatory biomarkers, suggesting associations between AF and inflammation is driven by acquired comorbidities rather than genetic predisposition.