efforts. Another important extension of an integrated model of BMI and obesity is to incorporate the moderating effects of the environment. At least two of the BMI-validated SNPs exhibit gene by environment interactions (GxE) [60, 61]. For example, a large meta-analysis found that in physically active adults the effect of the FTO risk allele on obesity was attenuated by 27% [62]. Given the considerable impact of the environment on body composition, future research needs to incorporate environmental variables into models of disease and risk prediction. Despite the potential limitations of the current study, this work provides a framework for integrating common and rare variation as both an alternative form of replication of genetic effects as well as for risk prediction of complex traits.
