BACKGROUND: Atrial fibrillation (AF) development is determined by clinical risk factors and genetic predisposition. Few studies have explored whether incorporating polygenic risk scores (PRS) improves clinical-risk prediction beyond existing models. OBJECTIVES: We evaluated the interaction between AF-PRS and the hypertension, age, raised body mass index, male sex, sleep apnea, and smoking-AF (HARMS METHODS: AF-PRS was examined in those with and without incident AF based on International Classification of Diseases, Tenth Revision coding and divided into tertiles defined as low, intermediate, and high-risk categories. Regression analysis examined the impact of AF-PRS combined with the HARMS RESULTS: Among 285,734 participants with available whole genome sequencing data (52% women, age 57 years [50-63], 84.6% Caucasian), AF incidence was 6.6% with a median time to AF 8.5 (5.0-11.2) over a median 12.9 years follow-up. High AF-PRS tertile was independently associated with incident AF risk, after adjustment for clinical-risk factors (hazard ratio 2.75, 95% confidence interval 2.62-2.89, P<
.002). AF-PRS enhanced AF risk prediction when combined with the HARMS CONCLUSIONS: Combining genetic and clinical risk using the HARMS