Influence of sleep duration on cumulative genetic effects on obesity and related anthropometric traits among preschool children.

OBJECTIVE: This study assesses the influence of genetic variations over 9 genes (FTO, CLOCK, ARNTL, CRP, IL6, NR3C1, LEP, GHRL, and ADIPOQ) involved in energy homeostasis and stress regulation on children's anthropometric traits and examines the impact of sleep duration on these genetic associations. METHODS: We analyzed 255 preschool children from Shanghai, China, and sequenced genetic variants from the nine candidate genes. Three genetic risk scores (GRS) were derived: GRS RESULTS: After adjusting for age, sex, and appetite with FDR correction, GRS CONCLUSIONS: Our findings suggest that genetic variants in the nine candidate genes, particularly those from FTO, LEP and GHRL, exert cumulative effects on anthropometric traits. GRS constructed from SNPs with modest effects can serve as a predictive tool for anthropometric outcomes and obesity risk, while GRS based on GWAS-identified SNPs can offer greater predictive power than GRS based on all eligible SNPs. Importantly, adequate sleep is essential for the manifestation of these genetic effects, whereas insufficient sleep may attenuate or mask them. These results highlight the importance of incorporating sleep as a key environmental factor in genetic studies and support personalized strategies for managing obesity risk in children.