Since obesity has increased dramatically while the genome has arguably remained stable, future research needs to address moderation effects of the environment. Known obesogenic factors such as physical activity and food intake have been shown to account for a significant portion of the variance in BMI with estimates ranging 5–10% (Chambers and Swanson 2010; Newby et al. 2006; French et al. 1994; Jebb and Moore 1999). Additionally, research is beginning to elucidate G×E affecting BMI (Rampersaud et al. 2008; Lappalainen et al. 2009; Qi et al. 2008; Brandsttter et al. 2009; Razquin et al. 2010). At least two genes included in the current GRSS show evidence for G×E effects. For example, Rampersaud et al. (2008), in a study of 704 Old Order Amish, found the effects of FTO variants associated with elevated body weight were attenuated in subjects with higher physical activity levels. Additionally, interactions between MCR4 and dietary intake and selection have been shown in model organisms (Fan et al. 1997; Huszar et al. 1997; Marsh et al. 1999; Chen et al. 2000). For example, mice when given a
