A large number of studies have shown that obesity is both under genetic control and influenced by several environmental factors, including energy expenditure and intake. Several studies in animals and humans have furthermore suggested that certain environmental factors, such as a high fat intake, may modify the expression of the genes responsible for weight gain. The present study examined whether physical activity, measured at the baseline examination in 1975, was likely to play a differential role in subsequent weight changes in the following 6 y in 1571 monozygotic and 3029 dizygotic, same-sex twin pairs from the Finnish Twin Cohort Study. A hierarchical multiple-regression analysis was used to test for gene-environment interactions by identifying significant three-way interactions between genetic factors, physical activity, and weight change. The results showed that associations between weight change in twin A and twin B were significantly stronger for monozygotic than for same-sex dizygotic twins at all levels of physical activity. Additionally, in the monozygotic men the strength of the association varied with physical activity level, and the association between the change in body mass index between the twin pairs with the highest physical activity level was about three times stronger (beta = 0.40) than the association in twin pairs with the lowest physical activity level (beta = 0.15, P for trend = 0.002). In pairs of dizygotic men, and in both monozygotic and dizygotic women, similarity in body mass index change was independent of physical activity level (all P > 0.14). The present study showed that genetic factors may modify the effects of physical activity on weight change, and suggests that a sedentary lifestyle may have an obesity-promoting effect in men with a genetic predisposition.
