Using Polygenic Scores for Circadian Rhythms to Predict Wellbeing, Depressive Symptoms, Chronotype, and Health

The association between circadian rhythms and diseases has been well established, while the association with mental health is less explored. Given the heritable nature of circadian rhythms, this study aimed to investigate the relationship between genes underlying circadian rhythms and mental health outcomes, as well as a possible gene-environment correlation for circadian rhythms. Polygenic scores (PGSs) represent the genetic predisposition to develop a certain trait or disease. In a sample from the Netherlands Twin Register (N = 14,021), PGSs were calculated for two circadian rhythm measures: morningness and relative amplitude (RA). 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 RA significantly predicted general health (R2 = 0.12%) and depressive symptoms (R2 = 0.20%). Item analysis of the depressive symptoms showed that 4 out of 14 items were significantly associated with the PGSs. Overall, the results showed that people with a genetic predisposition of being a morning person or with a high RA are likely to have fewer depressive symptoms. The four associated depressive symptoms described symptoms related to decision-making, energy, and feeling worthless or inferior, rather than sleep. Based on our findings future research should include a substantial role for circadian rhythms in depression research and should further explore the gene-environment correlation in circadian rhythms.