Tikkanen E, et al. - In this large observational study, researchers assessed independent causal roles of fat-free mass and fat mass on atrial fibrillation (AF). For this purpose, they used data from 487,404 subjects with 10,365 events in the UK Biobank. They obtained genetic instruments for Mendelian randomization (MR) via genome-wide association analysis. Using genetic associations from AFGen consortium as outcome, they assessed the causal impacts of fat-free mass and fat mass on AF via two-sample method. Using multivariate MR, they assessed independent causal effects of fat-free mass and fat mass. For fat-free mass and for fat mass, the observed causal effects using the inverse-variance weighted method were 1.55 and 1.30, respectively. Similar estimates were reproduced by using weighted median, Egger regression, and penalized methods. The causal effects of fat-free and fat mass were found independent of each other, as revealed in the multivariate MR analysis. Overall, genetically programmed elevations in fat-free mass and fat mass were found to independently lead to an increased risk of AF.