Using Polygenic Scores for Circadian Rhythm to predict Wellbeing, Depressive Symptoms, Chronotype, and Health

Abstract

AbstractThe 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.