These results collectively suggest that genetic influences on the development of obesity can be mitigated by environmental conditions. However, these data do not necessarily provide support for the presence of gene-by-environment interactions within the U.S. population at a single time period. As noted in Section 7, this represents an avenue for additional research, especially when considering the potential moderating effects of SES and environmental factors associated with lower income.

Genetic Factors as a Potential Moderator Variable

Bouchard and colleagues conducted a seminal “overfeeding” study in which 12 male MZ twin pairs were fed an additional 1,000 kcal/day beyond their baseline intake levels, for 6 days per week over 100 days [155]. The investigators tested whether changes in body composition in response to overfeeding differed as a function of twinship. Outcome measures included changes in body composition and metabolic parameters. Results provided clear evidence that response to overfeeding was related to twinship. Twins were significantly correlated with respect to changes in body weight, percent fat mass, fat mass, and estimated subcutaneous fat, and visceral adiposity. Table C-3 presents changes in study outcome measures associated with experimental overfeeding and the intraclass correlation coefficients representing the within-twin pair association for change scores.

In recent years, a series of candidate gene analyses evaluated whether specific genes were associated with response to overfeeding in this cohort. As reviewed by Ukkola and Bouchard [156], a number of candidate genes showed associations. For example, a polymorphism in the adipsin gene was associated with greater increases in body weight, total fat mass, and subcutaneous fat in response to overfeeding; the Gln27Glu polymorphism of the beta 2 adrenergic receptor gene was associated with greater gains in body weight and subcutaneous fat. Few associations were found for changes in visceral adiposity. Despite the limited sample size, these analyses have been critical to the field for demonstrating how specific genes might moderate the effects of a specific environmental manipulation that promotes weight gain (i.e., overfeeding).

Finally, Epstein et al. [157] recently reported that the association between the “reinforcing value of food” phenotype (see Section 5) and ad libitum energy intake in the laboratory was moderated by the dopamine transporter gene (SLC6A3) and the dopamine 2 receptor gene (DRD2). Participants were 88 smokers of European American ancestry who were evaluated before beginning a smoking cessation treatment. With respect to the SLC6A3 gene, subjects who scored high on the reinforcing value of food and who lacked the SLC6A3*9 allele consumed more total energy than participants with other SLC6A3 genotypes. With respect to the DRD2

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