OBJECTIVE: This study aimed to investigate the effect of a genetic risk score (GRS) comprising 15 single-nucleotide polymorphisms, previously shown to associate with childhood BMI, on the baseline cardiometabolic traits and the response to a lifestyle intervention in Danish children and adolescents. METHODS: Children and adolescents with overweight or obesity (n = 920) and a population-based control sample (n = 698) were recruited. Anthropometric and biochemical measures were obtained at baseline and in a subgroup of children and adolescents with overweight or obesity again after 6 to 24 months of lifestyle intervention (n = 754). The effects of the GRS were examined by multiple linear regressions using additive genetic models. RESULTS: At baseline, the GRS associated with BMI standard deviation score (SDS) both in children and adolescents with overweight or obesity (β = 0.033 [SE = 0.01]; P = 0.001) and in the population-based sample (β = 0.065 [SE = 0.02]; P = 0.001). No associations were observed for cardiometabolic traits. The GRS did not influence changes in BMI SDS or cardiometabolic traits following lifestyle intervention. CONCLUSIONS: A GRS for childhood BMI was associated with BMI SDS but not with other cardiometabolic traits in Danish children and adolescents. The GRS did not influence treatment response following lifestyle intervention.