FTO Obesity Variant–Exercise Interaction on Changes in Body Weight and BMI: The Taiwan Biobank Study

Abstract Context Gene–exercise interaction on cross-sectional body mass index (BMI) has been extensively studied and is well established. However, gene–exercise interaction on changes in body weight/BMI remains controversial. Objective To examine the interaction between the FTO obesity variant and regular exercise on changes in body weight/BMI. Participants Taiwan Biobank participants aged 30-70 years (N = 20 906) were examined at both baseline and follow-up visit (mean follow-up duration: 3.7 years). Main Outcome Measures The interaction between the FTO obesity variant rs1421085 and regular exercise habit (no exercise, ≤20 metabolic equivalent of tasks (METs)/week exercise, >20 METs/week exercise) on changes in body weight/BMI. Results Individuals with the risk allele of rs1421085 gained more weight and increased BMI than those without the risk allele if they did not exercise. In contrast, individuals with the risk allele gained less weight and BMI if they exercised regularly, indicating an interaction between rs1421085 and regular exercise habit (P = .030 for Δbody weight and P = .034 for ΔBMI). The effect of exercise on maintaining body weight was larger in those with the risk allele of rs1421085. When we focused on individuals without regular exercise at baseline, individuals with the risk allele again tended to lose more weight than those with a nonrisk allele if they had acquired an exercise habit by the follow-up visit. Conclusion The beneficial effect of exercise is greater in individuals genetically prone to obesity due to the interaction between the FTO obesity variant rs1421085 and regular exercise on changes in body weight and BMI.