Abstract 2178: Does Lifestyle Modify the Genetic Risk of Obesity? An Association Study of Lifestyle Interactions With FTO Genotype in 21,675 Caucasian Women
Background Variation in the FTO gene has been strongly associated with obesity in multiple populations but its mechanisms of action, and whether lifestyle factors can modify this associated genetic risk, remain unclear. We investigated whether the association of the rs8050136 risk allele (A) with obesity is mediated or modified by lifestyle patterns.
Methods 21,675 Caucasian women in the Women’s Genome Health Study were genotyped for the FTO rs8050136 variant. Physical activity (PA), caloric intake (CI), and obesity phenotypes were assessed by self-reported questionnaires. Results The FTO risk allele was significantly (p<0.001) associated with increased BMI and obesity-related phenotypes. The risk allele was not associated with PA or CI (p=0.51 and 0.81). The per-allele increase in mean BMI (±SE) was greater by ~2-fold in women with less than vs. those with greater than median levels of PA (0.73±0.1 vs. 0.3±0.1 kg/m2; p<0.0001) and similarly between those with greater vs. less than median levels of CI (0.65±0.1 vs. 0.38±0.1 kg/m2; p<0.0001). The per-allele increase in mean BMI (±SE) was greater by ~ 4-fold (0.97±0.1 vs. 0.22±0.1 kg/m2, p<0.0001) in inactive/high calorie women vs. active/low calorie women (figure⇓). Statistical tests for interaction were significant between the risk allele and both PA and CI (p<0.0001 and 0.005).
Conclusions There was significant modification of the genetic risk of the rs8050136 risk allele by lifestyle factors, with the strongest genetic effect noted in women with low levels of physical activity and high caloric intake. Healthier lifestyle patterns blunted, but did not completely eliminate, the associated genetic risk on obesity.