The association between the circadian rhythm and diseases has been well-established, while the association with mental health is less explored. Given the heritable nature of the circadian rhythm, this study aimed to investigate the relationship between genes underlying the circadian rhythm and mental health outcomes, as well as a possible gene-environment correlation for circadian rhythm. In a sample from the Netherlands Twin Register (N = 14,021), polygenic scores (PGSs) were calculated for two circadian rhythm measures: Morningess and Relative Amplitude. The PGSs were used to predict mental health outcomes such as subjective happiness, quality of life, and depressive symptoms In addition, we performed the same prediction analysis in a within-family design in a subset of dizygotic twins. The PGS for Morningness significantly predicted Morningness (R2 = 1.55%,) and Depressive Symptoms (R2= 0.22%,). The PGS for Relative Amplitude significantly predicted General Health (R2 = 0.12%,) and Depressive Symptoms (R2 = 0.20%,). Item analysis of the depressive symptoms showed that 4/14 items were significantly associated with the PGSs. The within-family results hinted at a gene-environment correlation for Morningness. Overall, the results showed that people with a genetic predisposition of being a morning person or a high relative amplitude are likely to have fewer depressive symptoms. Contrarily to our hypotheses, the four associated depressive symptoms described symptoms related to decision-making, energy, and feeling worthless, rather than sleep. Our findings plead for a substantial role for the circadian rhythm in depression research, and to further explore the gene-environment correlation in the circadian rhythm.

The authors have declared no competing interest.

This study was funded by the European Union's Horizon 2020 research and innovation programme under grant agreement no. 945238, and by an European Research Council (ERC) consolidator grant (WELL-BEING 771057 PI Bartels)

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Central Ethics Committee Research Involving Human Subjects of the VU University Medical Centre Amsterdam, an Institutional Review Board certified by the U.S. Office of Human Research Protections (IRB number IRB-2991 under Federal-wide Assurance-3703; IRB/institute codes, NTR 03-180) gave ethical approval for this work.

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All data produced in the present study are available upon reasonable request to the authors.