Genetic Pathways Underlying Individual Differences in Regular Physical Activity

Abstract

Twin and family studies show a strong contribution of genetic factors to physical activity (PA) assessed by either self-report or accelerometers. PA heritability is around 43% across the lifespan. Genome-wide association studies have implied biological pathways related to exercise ability and enjoyment. A polygenic score based on genetic variants influencing PA could help improve the success of intervention programs.

Exercise and Artery Function in Twins: Sex Differences in a Cross-Over Trial

“…An alternative approach compares the relative importance of shared environmental and genetic influences in monozygotic and dizygotic twin pairs. 12 This provides a platform to determine whether shared environment explains more variation than genetic influences, in which case looking for associations with specific genotypes is extremely difficult. In the current study, rMZ were typically high and rDZ very low, indicating that factors shared between monozygotic twins are important influences on training-induced changes in FMD% and GTN%.…”

“…35 The latter, genome-wide association, is less impacted by a priori bias but requires hundreds of thousands of participants to identify genetic variants in highly polygenic phenotypes. 12 Indeed, genome-wide association has demonstrated that the contribution of single variants to physiological outcomes is typically very small; 12,36 for example 9 single nucleotide polymorphisms may explain ≈2% of the variance in VO 2 max, while another 7 contribute only 1% to 2%. An alternative approach compares the relative importance of shared environmental and genetic influences in monozygotic and dizygotic twin pairs.…”

“…Differences between intraclass correlation coefficients for monozygotic and dizygotic twins (rMZ versus rDZ) were assessed using the likelihood-ratio test to compare the models constraining and not constraining covariances for monozygotic and dizygotic pairs to be equal. 12 If rMZ was significantly different to rDZ then A, C, E were calculated using the delta method. When rMZ and rDZ were not significantly different, a single model was used to calculate C and E components only.…”

“…The current study used a classical twin paradigm, 12 in a randomized cross-over design of distinct exercise modalities (endurance versus resistance training). We hypothesized (1) that vascular function responses would be modality-specific; (2) that a majority of individuals would respond similarly to both modes of training (ie, concordant responders would predominate); (3) that vascular responses to exercise would be sex-dependent; and (4) that vascular responses to each mode of training would express a high degree of heritability.…”

“…In general, it has been suggested that male and female sex hormones may differentially impact endothelial and vascular smooth muscle function. 10,11 Furthermore, the extent to which vascular responses to exercise training are heritable has not been comprehensively addressed; studies of monozygotic and dizygotic twins 12 have typically compared endothelial function 13,14 at a single-time point. 15 Such cross-sectional assessment may not reflect the heritability of exercise trainability, and data pertaining to exercise training effects on vascular function in twins are scarce.…”