Evidence for shared genetics between physical activity, sedentary behaviour and adiposity‐related traits

Abstract

Summary Observational, cross‐sectional and longitudinal studies showed that physical activity and sedentary behaviour are associated with adiposity‐related traits, apparently in a bidirectional manner. Physical activity is also suggested to suppress the genetic risk of adiposity. Since phenotypic associations with genetic variants are not subject to reverse causation or confounding, they may be used as tools to shed light on cause and effect in this complex interdependency. We review the evidence for shared genetics of physical activity and adiposity‐related traits and for gene‐by‐physical activity interactions on adiposity‐related traits in human studies. We outline limitations, challenges and opportunities in studying and understanding of these relationships. In summary, physical activity and sedentary behaviour are genetically correlated with body mass index and fat percentage but may not be correlated with lean body mass. Mendelian randomisation analyses show that physical activity and sedentary behaviour have bidirectional relationships with adiposity. Several studies suggest that physical activity suppresses genetic risk of adiposity. No studies have yet tested whether adiposity enhances genetic predisposition to sedentariness. The complexity of the comprehensive causal model makes the assessment of the single or combined components challenging. Substantial progress in this field may need long‐term intervention studies.

Association of Sedentary and Physical Activity Behaviors with Body Composition: a Genome-Wide Association and Mendelian Randomization Study

“…We identified a consistent positive association for BMI on self-reported sedentary behavior, while accelerometer-measured estimates of BMI on sedentary behavior were null. Similar to Shnurr et al (51), we did not identify an effect of genetically-predicted BMI on overall activity or MVPA. Overall, our findings conflicting with previous literature may have been driven by differing instrumental variable inclusion criteria, as was well as application of more conservative methodologies such as MVMR and CAUSE.…”

“…In contrast to our study, Doherty and colleagues used an accelerometer-measured overall activity exposure distinct from our own exposure, as well as a likelihood-based method to estimate causal effects. A MR meta-analysis from Shnurr et al (51) using a smaller cohort of both children and adults further suggested a positive association of BMI on sedentary time. We identified a consistent positive association for BMI on self-reported sedentary behavior, while accelerometer-measured estimates of BMI on sedentary behavior were null.…”

“…Therefore, efforts are needed to better elucidate the shared genetics and pathways that link PA with weight and body composition. (51) We applied MR using a comprehensive set of PA and body composition measures to increase confidence in causal estimations between PA and body composition, considering self-reported and accelerometer-based PA exposures in parallel analyses. Our results provide some evidence of a protective effect on VAT from genetically-predicted levels of accelerometer-measured MVPA and vigorous PA, as well as self-reported SSOE.…”

Interactions of physical activity, muscular fitness, adiposity, and genetic risk for NAFLD

“…Strengths of the present study include the large number of individuals with genetic and objectively assessed physical activity and grip strength, collected as part of the UK Biobank, in which the same protocol was used for all participants. [ 39 ] Applying a GRS based on a larger, more comprehensive set of NAFLD associated genetic variants may have a greater statistical power to detect gene–lifestyle interactions [ 39 , 40 , 41 ] compared with single SNPs and smaller GRSs used in the previous studies. [ 15 , 16 , 17 ] We used external weights, the gold standard, for the construction of the GRS [ 42 ] by computing the weighted GRS based on weights for each genetic marker as derived by GWAS in the Million Veteran Program.…”

Learning From Human Responses to Deconditioning Environments: Improved Understanding of the “Use It or Lose It” Principle

“…This sedentary behavior plus obesity can have severe detrimental effects on the integrity of the MSK and cardiovascular systems for both adults and those undergoing growth and maturation, particularly as these conditions become chronic (Elagizi et al, 2020 ; Kanellopoulou et al, 2021 ). There is also some evidence for the shared interaction between these variables at the genetic level (Schnurr et al, 2021 ).…”