Childhood sleep duration modifies the polygenic risk for obesity in youth through leptin pathway: the Beijing Child and Adolescent Metabolic Syndrome cohort study

• Published in: International Journal of Obesity Vol. 43; no. 8; pp. 1556 - 1567
• Main Authors: Fu, Junling, Wang, Yonghui, Li, Ge, Han, Lanwen, Li, Yu, Li, Lujiao, Feng, Dan, Wu, Yunpeng, Xiao, Xinhua, Li, Mingyao, Grant, Struan F. A., Li, Ming, Gao, Shan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2019; Nature Publishing Group
• Subjects: 38/47; 38/77; 692/163/2743/2037; 692/163/2743/393; 96/21; Ablation; Adolescent; Adolescents; Body mass index; Body size; Body weight; Child; Childhood; Children; China; Cohort analysis; Cohort Studies; Epidemiology; Female; Follow-Up Studies; Gene-Environment Interaction; Genetic aspects; Genetic Predisposition to Disease; Health aspects; Health Promotion and Disease Prevention; Humans; Internal Medicine; Leptin; Leptin - metabolism; Male; Mediation; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - genetics; Multifactorial Inheritance; Obesity; Obesity in adolescence; Obesity in children; Overweight; Pathogenesis; Pediatric Obesity - genetics; Pediatric Obesity - metabolism; Pediatric Obesity - psychology; Polygenic inheritance; Public Health; Risk analysis; Risk Factors; Single-nucleotide polymorphism; Sleep; Sleep - physiology; Teenagers; Time Factors; Youth; China; Beijing China
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/s41366-019-0405-1

Background/objectives Short sleep is an obesity risk factor, however, little is known about its interplay with genetic predisposition and pathways involved in obesity pathogenesis, especially in the longitudinal setting. We aimed to investigate a possible sleep-gene interaction for childhood obesity risk, and whether the interaction in childhood longitudinally contributes to obesity risk at a 10-year follow-up and further to test if there is any mediation through the leptin pathway. Subjects/methods A total of 3211 children from China (6–18 years) at baseline and 848 participants at 10-year follow-up from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) cohort study were analyzed. Baseline leptin concentrations and 12 established adult body mass index (BMI) loci were examined for the associations with habitual sleep duration. Results After adjusting for covariates, including pubertal stages and behavioral factors, short sleep duration at baseline was significantly associated with increased overweight/obesity risk at both baseline and follow-up. Genetic predisposition scores (GPS), particularly consisting of leptin-related SNPs (GPS leptin ), were robustly associated with baseline overweight/obesity in children who slept ≤8 h/day ( P   <  0.001), whereas the association was ablated in those who slept ≥10 h/day ( P   >  0.05). Comparable observations were made at follow-up. Mediation analysis revealed a modest direct effect of the GPS leptin -sleep interaction on BMI at baseline, while a significant indirect effect of this interaction was found to be mediated principally through elevated leptin (proportion: 52.6%); moreover, the mediation effect via leptin remained stable over 10 years. Conclusions This study suggests that shorter sleep duration in children from China (< 8h/day), compared to longer sleep duration (≥10 h/day), has a long-term impact on the association of polygenic risk for obesity from childhood to young adulthood and leptin pathway explains a key mechanism via a modification effect. Therefore, adequate sleep duration during childhood is important for the early prevention of obesity, especially if there is a genetic predisposition to this trait.