Body Weight and Adiposity
In the past five reviews, we reported on the growing evidence that the genetic susceptibility to obesity is attenuated by 20%–40% in adults who are physically active compared to those who are inactive, suggesting that even those who are genetically predisposed to gain weight more easily do benefit from an active lifestyle. The genetic susceptibility was typically assessed by either an SNP in FTO or by combining multiple body mass index (BMI)–associated loci, predominantly those discovered before 2010, into a genetic risk score (GRS). The studies we described were large, including 20,000 to more than 200,000 individuals, thus providing sufficient power and convincing evidence.
New studies reported in 2014 offered mainly corroborating observations but including obesity-associated loci reported in 2010 and using longitudinal study designs. For example, a population-based study of 2894 Han Chinese adults found that the BMI-increasing effect of a GRS, comprised of 28 BMI-associated variants, was reduced by 60% (Pinteraction = 0.022) in individuals with high physical activity levels compared to individuals with low physical activity levels. The longitudinal 1946 British Birth Cohort, which followed 2444 men and women from birth up to age 64 yr, found that the genetic susceptibility assessed by a GRS of 11 BMI-associated loci was significantly (Pinteraction = 0.004) attenuated by physical activity from age 53 yr onward, despite the fact that "being active" was loosely defined as participation in sports activities at least once a month. A Danish study of 3982 individuals (mean [SD] age at baseline 46.7 [7.7] yr), who were followed for 5 yr, examined whether a GRS based on 30 BMI-associated variants associated with change in BMI over time, and whether change in physical activity during the same period influences that association. The GRS, whereas significantly associated with baseline BMI, was not associated with change in BMI during the following 5 yr, and changes in physical activity levels during that timeframe had no effect on the GRS-BMI change association, which is consistent with previous observations using a similar design. A longitudinal design has the advantage that it controls for reverse causation, but the downside is that it requires a larger sample to convincingly refute or prove interaction between genes and environment. The National Longitudinal Study of Adolescents studied 7642 participants at the age of 16 yr and found no evidence of an interaction between screen time and genetic susceptibility to obesity in adolescence. This is consistent with the observation of a large-scale meta-analysis (n > 19,000) that found that the BMI-increasing effect of FTO was the same in physical active and physically inactive children and adolescents. We have speculated before that the lack of interaction may be due to a weak association between physical activity and BMI and the relatively higher levels of physical activity in childhood and adolescence.
Whereas the evidence that physical activity attenuates the genetic susceptibility to obesity is growing, in particular in adults, it remains unclear whether the attenuation is due to specific properties of physical activity as such, or whether a healthy lifestyle in general would induce similar attenuating effects. Recent large-scale studies examining the effect of dietary factors, as another proxy of a healthy lifestyle, on the association between genetic variants and obesity traits have been inconclusive. For example, a large-scale study (n > 37,000) found that the association between a GRS and BMI was significantly weaker in individuals who consumed a healthier diet (less fried food and sugar-sweetened beverages) compared to those who consumed more of the unhealthy foods. However, a meta-analysis including data from more than 177,000 individuals found no evidence that FTO's BMI-increasing effect is attenuated by dietary intakes. Similarly, the genetic susceptibility to obesity, assessed by a GRS of 16 loci, in more than 29,000 Swedish individuals was not influenced by dietary intake.
In summary, the beneficial effect of physical activity on the genetic susceptibility to obesity in adults continues to gain strength. It remains to be determined whether this is due to effects specific to physical activity or whether this is due to a healthy lifestyle in general. Furthermore, new findings confirm that the attenuating effects of physical activity only appear in (later) adulthood.