The Q223R Polymorphism of the Leptin Receptor Gene as a Predictor of Weight Gain in Childhood Obesity and the Identification of Possible Factors Involved

(1) Background: Childhood rapid weight gain during development has been postulated as a predictor of obesity. The objective of this study was to investigate the effect of single nucleotide polymorphisms (SNPs) on the annual weight gain and height growth, as well as identifying possible lifestyle factors involved. (2) Methods: As part of the GENYAL study, 221 children (6–8 years old) of Madrid (Spain) were enrolled. A total of 11 SNPs associated with high childhood body mass indexes (BMIs) were assessed. Anthropometric measurements, dietary and physical activity data, were collected in 2017 and 2018. Bonferroni-corrected linear models were used to fit the data. (3) Results: A significant association between the Q223R LEPR and the weight growth was found, showing a different behavior between GA and GG genotypes (p = 0.001). Regarding lifestyle factors, an interaction between Q223R genotypes and total active weekly hours/week to predict the weight growth (kg/year) was observed (p = 0.023). In all the genotypes, a beneficial effect against rapid weight growth was observed, but the effect size of the interaction was much more significant in homozygous (GG) minor homozygous (β = −0.61 (−0.95, −0.26) versus heterozygous (AG) and wild-type homozygous (AA) genotypes (β = −0.07 (−0.24, 0.09) and β = −0.12 (−0.32, 0.08), respectively). (4) Conclusions: These results may contribute to more personalized recommendations to prevent childhood obesity.