Hernandez Leanna M, Amirtha Ganesh Sai Sruthi, Gandal Michael J, Fuligni Andrew J
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
Departments of Psychiatry and Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sleep. 2025 Jun 13;48(6). doi: 10.1093/sleep/zsaf094.
Adolescence is characterized by later sleep onset and wake times, indicating a shift to an evening chronotype. Genome-wide association studies (GWAS) in adults show chronotype is polygenic and causally linked to depression, schizophrenia, and cognitive function. Yet, the impact of genetics on adolescent chronotype remains largely unexplored, and biological factors influencing the predictive relationship between genetics and chronotype have not been well-defined. This study aims to assess the utility of polygenic scores (PGS) derived from adult GWAS in predicting adolescent chronotype, mental health, and cognition while considering sex- and puberty-dependent effects.
Generalized linear models were used to assess the relationship between PGS for chronotype and self-reported chronotype, mental health, and cognition in 2411 youths of European ancestry aged 10-13 years. Interaction terms assessed whether the genotype-phenotype relationships varied by sex or pubertal development. Statistical significance was determined using a likelihood ratio test.
Significant sex- and puberty-dependent effects were observed. Higher PGS for morningness concordantly predicted earlier self-reported chronotype, but in female youth only. Follow-up analyses showed that sex-specific effects were mediated by the interaction between PGS and pubertal status. Greater genetic predisposition for morningness was negatively associated with somnolence and cognition in males and negatively associated with psychotic-like experiences in females.
The influence of genetic predisposition for early versus late chronotype on adolescent sleep-wake behavior emerges as puberty progresses. These findings suggest puberty is a critical transition when genetic variants associated with chronotype in adults become relevant to pediatric cohorts.
青春期的特点是入睡时间和起床时间较晚，表明向晚睡时型转变。成人全基因组关联研究（GWAS）表明，时型是多基因的，与抑郁症、精神分裂症和认知功能存在因果联系。然而，遗传学对青少年时型的影响在很大程度上仍未得到探索，影响遗传学与青少年时型预测关系的生物学因素也尚未明确界定。本研究旨在评估源自成人GWAS的多基因分数（PGS）在预测青少年时型、心理健康和认知方面的效用，同时考虑性别和青春期相关影响。
使用广义线性模型评估2411名10 - 13岁欧洲血统青少年中，时型PGS与自我报告的时型、心理健康和认知之间的关系。交互项用于评估基因型与表型的关系是否因性别或青春期发育而有所不同。使用似然比检验确定统计学显著性。
观察到显著的性别和青春期相关影响。晨型的较高PGS一致地预测了较早的自我报告时型，但仅在女性青少年中如此。后续分析表明，性别特异性影响是由PGS与青春期状态之间的相互作用介导的。男性中，较高的晨型遗传易感性与嗜睡和认知呈负相关，女性中则与类精神病体验呈负相关。
随着青春期的进展，早时型或晚时型的遗传易感性对青少年睡眠 - 觉醒行为的影响逐渐显现。这些发现表明，青春期是一个关键的过渡阶段，此时与成人时型相关的基因变异对儿科队列变得至关重要。
