The combination of physical activity and sedentary behaviors modifies the genetic predisposition to obesity

Objective:\ud \ud This study aimed to investigate whether the association between a validated genetic profile risk score for BMI (GPRS‐BMI) (based on 93 single‐nucleotide polymorphisms) and phenotypic obesity (BMI) was modified by the combined categories of physical activity (PA) and sedentary behaviors in a large population‐based study.\ud Methods:\ud \ud This study included cross‐sectional baseline data from 338,216 white European adult men and women aged 37 to 73 years. Interaction effects of GPRS‐BMI with the combined categories of PA and sedentary behaviors on BMI were investigated.\ud Results:\ud \ud There was a significant interaction between GPRS‐BMI and the combined categories of objectively measured PA and total sedentary behavior (P[interaction] = 3.5 × 10−6); among physically inactive and highly sedentary individuals, BMI was higher by 0.60 kg/m2 per 1‐SD increase in GPRS‐obesity (P = 8.9 × 10−50), whereas the relevant BMI difference was 38% lower among physically active individuals and those with low sedentary time (β: 0.37 kg/m2; P = 2.3 × 10−51). A similar pattern was observed for the combined categories of objective PA and TV viewing (inactive/high TV viewing β: 0.60 vs. active/low TV viewing β: 0.40 kg/m2; P[interaction] = 2.9 × 10−6).\ud Conclusions:\ud \ud This study provides evidence that combined categories of PA and sedentary behaviors modify the extent to which genetic predisposition to obesity results in higher BMI.