To examine the sources of heterogeneity between studies, which was moderate (I 2 = 36%) (Table 2; Figure 2), we used meta-regression. The meta-regression indicated heterogeneity by geographic region (North America versus Europe) in the interaction (p = 0.001) (Tables S4 and S5). When we subsequently stratified our meta-analysis by geographic region, the attenuating effect of PA on the association between the FTO variant and BMI was more pronounced in North American populations than in European populations (p difference = 5×10−6) (Table 2; Figure 2). More specifically, the BMI-increasing effect of the FTO risk allele in physically active North Americans was 59% smaller than in inactive North Americans (beta = 0.34 versus 0.82 kg/m2, respectively), whereas the attenuation in the BMI-increasing effect of the risk allele in physically active Europeans compared with inactive Europeans was only 19% (beta = 0.30 versus 0.37 kg/m2, respectively) (Table 2). There was no heterogeneity among North American studies (I 2 = 0%), whereas moderate heterogeneity was observed among European studies (I 2 = 26%) (Table 2; Figure 2). In a further sub-group meta-regression, none of the covariates explained a significant proportion of the remaining heterogeneity observed in Europeans.
