Physical fitness attenuates the genetic predisposition to obesity in children and adolescents.

Obesity is an important risk factor associated with non-communicable cardiometabolic diseases. Previous studies have indicated that children and adolescents with a predisposed genetic risk for obesity could benefit from an active lifestyle, but there are no studies investigating whether physical fitness moderates the association of genetics and obesity. The aim of this study was to verify the moderating role of physical fitness in the relationship between genetic risk score (GRS) and body mass index (BMI) in children and adolescents. This cross-sectional study was carried out with 1471 children and adolescents, aged between 6 and 17 years from Santa Cruz do Sul, Brazil. Weight and height were assessed to determine BMI. Physical fitness components (cardiorespiratory fitness [CRF], lower limb strength [LLS], upper limb strength, and abdominal strength) were evaluated. The GRS was based on previously associated obesity single-nucleotide polymorphism rs9939609 (FTO), rs6548238 (TMEM18), and rs16835198 (FNDC5). Moderation analyses were tested using linear regression models, and the interactions were represented by physical fitness components X GRS (categorical variable). All analyses were adjusted for skin color/ethnicity, sex, and sexual maturation. Significant interactions for CRF (P = 0.041), LLS (P = 0.041), and abdominal strength (P = 0.046) X 5 and 6 risk alleles with BMI were found only in adolescents. In addition, there was evidence that fitness components attenuated the high genetic predisposition to high BMI. Physical fitness components are moderators in the relationship between GRS and BMI in adolescents. These findings highlight the need for interventions targeting to improve this aspect, which is an important health indicator in all ages.