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

Area of Science:

• Genetics
• Chronobiology
• Psychiatry

Background:

• Circadian rhythms are linked to diseases, but their connection to mental health is less understood.
• Circadian rhythms have a heritable component, suggesting a genetic influence on their regulation.
• Polygenic scores (PGSs) can quantify an individual's genetic predisposition for specific traits.

Purpose of the Study:

• To investigate the relationship between genetic variations in circadian rhythms and mental health outcomes.
• To explore potential gene-environment correlations influencing circadian rhythms.
• To assess if PGSs for circadian traits can predict mental health indicators.

Main Methods:

• Calculated PGSs for morningness and relative amplitude (RA) in a large twin registry (N=14,021).
• Predicted mental health outcomes (subjective happiness, quality of life, depressive symptoms) using these PGSs.
• Conducted within-family analyses using dizygotic twins to validate findings.

Main Results:

• PGS for morningness predicted morningness (R²=1.55%) and depressive symptoms (R²=0.22%).
• PGS for RA predicted general health (R²=0.12%) and depressive symptoms (R²=0.20%).
• Specific depressive symptoms related to decision-making, energy, and self-worth were associated with circadian rhythm PGSs.

Conclusions:

• Genetic predisposition towards morningness or higher circadian rhythm amplitude is associated with reduced depressive symptoms.
• Circadian rhythm genetics play a role in mental well-being, particularly in specific depressive symptom clusters.
• Future research should integrate circadian rhythms into depression studies and investigate gene-environment interactions.