Paper Information

We did not identify consistent associations between genetically predicted self-reported and accelerometer-measured sedentary behaviour 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% CI: -0.24 to -0.07, p<0.001) and self-reported participation in strenuous sports or other exercises (MVMR β=-0.27, 95% CI: -0.52 to -0.01, p=0.034) was robust across several sensitivity analyses.

) and visceral adipose tissue (VAT) (kg).

We 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.

Genetic instruments were identified for both self-reported and accelerometer-measured sedentary behaviour 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.