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Summary: Numerous guidelines have called for personalized interventions to address childhood obesity. The role of fat mass and obesity‐associated gene (FTO) in the risk of childhood obesity has been summarized. However, it remains unclear whether FTO could influence individual responses to obesity interventions, especially in children. To address this, we systematically reviewed 12,255 records across 10 databases/registers and included 13 lifestyle‐based obesity interventions (3980 children with overweight/obesity) reporting changes in body mass index (BMI) Z‐score, BMI, waist circumference, waist‐to‐hip ratio, and body fat percentage after interventions. These obesity‐related outcomes were first compared between children carrying different FTO genotypes (rs9939609 or its proxy) and then synthesized by random‐effect meta‐analysis models. The results from single‐group interventions showed no evidence of associations between FTO risk allele and changes in obesity‐related outcomes after interventions (e.g., BMI Z‐score: −0.01; 95% CI: −0.04, 0.01). The results from controlled trials showed that associations between the FTO risk allele and changes in obesity‐related outcomes did not differ by intervention/control group. To conclude, the FTO risk allele might play a minor role in the response to obesity interventions among children. Future studies might pay more attention to the accumulation effect of multiple genes in the intervention process among children. [ABSTRACT FROM AUTHOR]

Multiple lifestyle-based childhood obesity interventions have been conducted to address childhood obesity, but individual's response to the universal intervention approach varied greatly. Whether gene variants related to children and adolescents' varied responses to obesity interventions remained unclear. To determine the associations of gene variants with the changes in obesity- and metabolism-related indicators after obesity interventions in children and adolescents. Ten databases and registers (including grey literature) were searched. The lifestyle-based obesity interventions in children and adolescents (≤18 years) that reported the changes in obesity- (body mass index (BMI), BMI Z-score, waist circumference (WC), waist-to-hip ratio (WHR), etc) and metabolism-related (glucose, cholesterol, etc) indicators by genotype after interventions were included. Our primary outcome was the mean difference of the changes in BMI Z-score by genotype after interventions, and secondary outcomes were changes in the remaining obesity- and metabolism-related indicators after interventions. We used the random-effects model to synthesize the results. This review included 50 studies (15,354 children and adolescents with overweight/obesity) covering 102 genes and 174 single nucleotide polymorphisms (SNPs). Approximately three-quarters of SNPs showed no evidence of association with the changes in obesity- or metabolic-related indicators after interventions. One quarter of SNPs were minorly associated with the changes in the BMI Z-score (median effect size: 0.001) with little clinical significance. Only 6 (12 %) studies focused on the accumulated effect of multiple gene variants. Gene variants that have been explored appear to play a minor role in lifestyle-based obesity interventions in children and adolescents. More high-quality studies based on the design of randomized controlled trials are needed to examine the accumulated effect of multiple gene variants in childhood obesity interventions. This systematic review and meta-analysis was registered at PROSPERO as CRD42022312177. [ABSTRACT FROM AUTHOR]