Association between genetic risks and body mass index in occurrence of atrial fibrillation

Abstract Background Atrial fibrillation (AF) is influenced by both genetic predisposition and modifiable risk factors, such as body mass index (BMI). While obesity is a well-established risk factor for cardiovascular diseases, the interaction between BMI categories and genetic risk on the development of AF remains poorly understood. This study aims to investigate the relationship between BMI and polygenic risk scores (PRS) for AF. Methods This retrospective analysis involved data from the UK Biobank cohort to examine the interaction between BMI categories (underweight, normal weight, overweight, and obese) and PRS for AF. Participants were stratified into high and low genetic risk groups based on their PRS, and Kaplan-Meier survival analyses were performed to estimate AF incidence across BMI categories in each genetic risk group. The association between BMI and AF was further assessed using Cox proportional hazards models. Results Of the 477,418 subjects, 47,738 were classified as low genetic risk. While the AF event rate increased with obesity in the other genetic risk groups, in the low risk group, underweight individuals had a higher AF event rate compared to those who were overweight (P for trend <0.001). Additionally, the cumulative incidence of AF among underweight participants in the low risk group was similar to that of obese individuals. In the overall cohort, underweight was not associated with an increased risk of AF. However, when stratified by genetic risk, underweight appeared to be a significant predictor for AF in the low genetic risk group (HR: 2.69, 95% CI: 1.33–5.45). Conclusion In individuals with low genetic risk, underweight status may increase AF susceptibility, while in those with high genetic risk, genetic factors dominate AF risk irrespective of BMI.Cumulative incidence of AF according to Longitudinal association between BMI cat