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Triangulation across the results from genetically informative designs supports the existence of causal effects of exercise on mental health as well as residual confounding by genetic factors that independently influence participation in regular exercise and mental health outcomes.
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A model explaining the heritability of voluntary exercise behavior in terms of genetic moderation of its positive mental health effects can explain how causal effects co-exist with genetic pleiotropy.
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The model calls for further research with strategies that use genomic information to improve the success of interventions on regular exercise behavior.
Regular exercise is associated with mental health throughout the life course but the chain-of-causality underlying this association remains contested. I review results from genetically informative designs that examine causality, including the discordant monozygotic twin design, multivariate genetic models, Mendelian Randomization, and stratification on polygenic risk scores. Triangulation across the results from these and the standard designs for causal inference (RCT, prospective studies) in the extant literature supports the existence of causal effects of exercise on mental health as well as residual confounding by genetic factors that independently influence participation in regular exercise and mental health outcomes. I present an update of our earlier model for the genetic determinants of voluntary exercise behavior. The model allows causal effects of regular exercise on mental health to co-exist with genetic pleiotropy through differences in the genetic sensitivity to the mental health benefits of exercise. The model encourages research on strategies that use genomic information to improve the success of interventions on regular exercise behavior.
[Keywords: twin study, Mendelian Randomization, polygenic risk score, exercise psychology, personalized medicine]
