Objectives To investigate whether objectively measured physical activity (PA) modulates the association between the FTO rs9939609 polymorphism and obesity variables in a sample of Portuguese children.

Methods A total of 440 children (213 girls and 227 boys) aged 3 to 11 years were observed. Genotyping was performed using TaqMan assay. Body mass index (BMI), BMI Z scores, waist circumference (WC), and waist‐to‐height ratio (WHtR) were calculated. PA was estimated in 399 children by accelerometry.

Results Linear regression, in the additive model, showed that the rs9939609 minor A‐allele significantly associated with BMI (P = .029), BMI Z score (P = .017), WC (P = .016), and WHtR (P = .019). Logistic regression, in the additive model, showed a marginally significant association between the A‐allele and overweight/obesity (odds ratio [OR]: 1.372; P = .049). When stratified by sex, rs9939609 showed marginal or significant associations with BMI (P = .08), BMI Z score (P = .07), WC (P = .005), WHtR (P = .02), and overweight/obesity (OR: 1.529; P = .064) in girls but not in boys (P > .05). Significant interactions were not found between the FTO polymorphism and PA (inactive vs active groups of children) for BMI (P = .461), BMI Z score (P = .387), WC (P = .757), or WHtR (P = .621).