TY - JOUR T1 - Association of sedentary and physical activity behaviours with body composition: a genome-wide association and Mendelian randomisation study JF - BMJ Open Sport & Exercise Medicine JO - BMJ OPEN SP EX MED DO - 10.1136/bmjsem-2021-001291 VL - 8 IS - 3 SP - e001291 AU - Ferris A Ramadan AU - Jennifer W Bea AU - David O Garcia AU - Katherine D Ellingson AU - Robert A Canales AU - David A Raichlen AU - Yann C Klimentidis Y1 - 2022/08/01 UR - http://bmjopensem.bmj.com/content/8/3/e001291.abstract N2 - Objectives Studies suggest that body composition can be independently improved through physical activity (PA). We performed a Mendelian randomisation (MR) study to test the incremental benefits of sedentary behaviour and various PA exposures on body composition outcomes as assessed by anthropometric indices, lean body mass (kg), body fat (%) and visceral adipose tissue (VAT) (kg).Methods 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.Results 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.Conclusions 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.Data may be publicly available from a third party. Summary statistics from the GEnetic Factors for OSteoporosis (GEFOS) consortium, the Genetic Investigation of ANthropometric Traits (GIANT) consortium, self-reported sedentary behaviour and total body fat per cent are publicly available. Summary statistics for physical activity, educational attainment and visceral adipose tissue were obtained from the UK Biobank and are not publicly available. ER -