Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms

Summary

This large-scale genome-wide association study identified 351 genetic loci associated with chronotype in nearly 700,000 individuals, substantially expanding the known genetic architecture of circadian rhythm preference from 24 previously identified loci. The study demonstrated that identified genetic variants are enriched in circadian regulation, cAMP, glutamate and insulin signalling pathways, and are preferentially expressed in tissues central to circadian control (retina, hindbrain, hypothalamus, pituitary). Mendelian randomisation analyses provided evidence that a morning chronotype is causally associated with improved mental health, but showed no causal effect on BMI or type 2 diabetes risk.

UK applicability

The findings are directly applicable to UK populations, as UK Biobank participants comprised a substantial proportion of the study cohort. The insights into genetic determinants of circadian rhythm and their relationship to mental health may inform future preventive health strategies in the United Kingdom, though the absence of causal effects on metabolic traits limits immediate clinical implications for obesity or diabetes prevention.

Key measures

Chronotype phenotype (morning versus evening preference); genome-wide genetic variants; objectively measured sleep timing from activity monitors (n=85,760); mental health outcomes; BMI; type 2 diabetes risk

Outcomes reported

The study identified 351 genetic loci associated with chronotype (morning person tendency) using genome-wide association analysis in 697,828 participants, and demonstrated that these loci associate with objectively measured sleep timing differences of approximately 25 minutes between extreme allele carriers. Mendelian randomisation analyses were used to investigate causal associations between chronotype and mental health, body mass index, and type 2 diabetes risk.

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