A genetic perspective on the association between exercise and mental health in the era of genome-wide association studies

https://doi.org/10.1016/j.mhpa.2020.100378Get rights and content
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Highlights

  • Triangulation across genetically informative designs supports causal effects of exercise behaviour on mental health.

  • These causal effects co-exist with genetic correlation between exercise behaviour and mental health.

  • Genetic moderation of positive mental health effects explains how causal effects co-exist with genetic pleiotropy.

  • Research strategies using genomic information are needed to improve the success of interventions on exercise behaviour.

Abstract

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 behaviour. 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 behaviour.

Keywords

Twin study
Mendelian randomization
Polygenic risk score
Exercise psychology
Personalised medicine

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