Association of Sedentary and Physical Activity Behaviors with Body Composition: a Genome-Wide Association and Mendelian Randomization Study

ObjectivesStudies suggest that body composition can be independently improved through physical activity (PA). We performed a Mendelian randomization (MR) study to test the incremental benefits of sedentary behavior and various physical activity (PA) exposures on body composition outcomes as assessed by anthropometric indices, lean body mass (LBM) (kg), body fat (%), and visceral adipose tissue (VAT) (kg).MethodsGenetic instruments were identified for both self-reported and accelerometer-measured sedentary behavior and PA. Outcomes included anthropometric and dual-energy X-ray absorptiometry measures of adiposity, extracted from the UK Biobank and the largest available consortia. Multivariable MR (MVMR) included educational attainment as a covariate to address potential confounding. Sensitivity analyses were evaluated for weak instrument bias and pleiotropic effects.ResultsWe did not identify consistent associations between genetically-predicted self-reported and accelerometer-measured sedentary behavior and body composition outcomes. All analyses for self-reported moderate PA were null for body composition outcomes. Genetically-predicted PA at higher intensities was protective against VAT in MR and MVMR analyses of both accelerometer-measured vigorous PA (MVMR β = -0.15, 95% Confidence Interval (CI): -0.24, -0.07, pβ = -0.27, 95%CI: -0.52, -0.01, p=0.034) was robust across several sensitivity analyses.ConclusionsWe did not identify evidence of a causal relationship between genetically-predicted PA and body composition, with the exception of a putatively protective effect of higher-intensity PA on VAT. Protective effects of PA against VAT may support prior evidence of biological pathways through which PA decreases risk of downstream cardiometabolic diseases.