• Francesco Casanova, Jessica O'Loughlin, Vasilis Karageorgiou, Robin N Beaumont, Jack Bowden, Andrew R Wood, and Jessica Tyrrell.
• Genetics of Complex Traits, Department of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK.
• Bmc Med. 2023 Dec 18; 21 (1): 501501.

BackgroundMental health conditions represent one of the major groups of non-transmissible diseases. Physical activity (PA) and sedentary time (ST) have been shown to affect mental health outcomes in opposite directions. In this study, we use accelerometery-derived measures of PA and ST from the UK Biobank (UKB) and depression, anxiety and well-being data from the UKB mental health questionnaire as well as published summary statistics to explore the causal associations between these phenotypes.MethodsWe used MRlap to test if objectively measured PA and ST associate with mental health outcomes using UKB data and summary statistics from published genome-wide association studies. We also tested for bidirectional associations. We performed sex stratified as well as sensitivity analyses.ResultsGenetically instrumented higher PA was associated with lower odds of depression (OR = 0.92; 95% CI: 0.88, 0.97) and depression severity (beta =  - 0.11; 95% CI: - 0.18, - 0.04), Genetically instrumented higher ST was associated higher odds of anxiety (OR = 2.59; 95% CI: 1.10, 4.60). PA was associated with higher well-being (beta = 0.11, 95% CI: 0.04; 0.18) and ST with lower well-being (beta =  - 0.18; 95% CI: - 0.32, - 0.03). Similar findings were observed when stratifying by sex. There was evidence for a bidirectional relationship, with higher genetic liability to depression associated with lower PA (beta =  - 0.25, 95% CI: - 0.42; - 0.08) and higher well-being associated with higher PA (beta = 0.15; 95% CI: 0.05, 0.25).ConclusionsWe have demonstrated the bidirectional effects of both PA and ST on a range of mental health outcomes using objectively measured predictors and MR methods for causal inference. Our findings support a causal role for PA and ST in the development of mental health problems and in affecting well-being.© 2023. The Author(s).

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