A primary finding of this study is that of a gene×environment interaction between variants in the FTO gene and physical activity. Using objective-, age-, and sex-adjusted physical activity measures obtained for 7 consecutive 24-hour days, we were able to investigate the genotype associations of FTO variants in OOA subjects with high and low physical activity levels. Unlike questionnaires, the Actical device provides an objective estimate of physical activity that is unaffected by study participant recall bias. We found that SNP associations with BMI and related measures were limited to less physically active individuals. In the less active group, being AA homozygous for the rs1861868 FTO variant was associated with an increase in BMI of 2.1, a slightly higher estimate than that obtained by Frayling et al1 for rs9939609 in United Kingdom (UK) Wellcome Trust Case Control subjects with type 2 diabetes mellitus, and much higher than the same group’s estimate for rs9939609 in UK type 2 diabetes mellitus genetics consortium controls.1 By contrast, in the more physically active OOA stratum, the associations of the FTO variants were much smaller and
