Genetic prediction of early adolescent chronotype: effects of sex and pubertal status.

STUDY OBJECTIVES

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.