Depression and Bipolar Disorder Subtypes Differ in their Genetic Correlations with Biological Rhythms

Abstract Major Depression and Bipolar Disorder Type I (BIP-I) and Type II (BIP-II), are mood disorders characterized by the occurrence of depressed, manic, and hypomanic episodes in which specific changes of physical activity, circadian rhythm, and sleep are observed. While it is known that genetic factors contribute to variation in both mood disorders and these biological rhythms, it is an open question to what extent there is an overlap between their underlying genetics.Here, we used data from genome-wide association studies to examine the genetic relationship between mood disorders and biological rhythms. Linkage Disequilibrium Score Regression was applied to test the genetic correlation of depression, BIP-I, and BIP-II with physical activity (overall physical activity, moderate activity, sedentary behaviour), circadian rhythm (relative amplitude), and sleep features (sleep duration, daytime sleepiness). Furthermore, we compared depression, BIP-I, and BIP-II in their correlations with biological rhythms to discover commonalities and differences. Depression was negatively correlated with overall physical activity and positively with sedentary behaviour, while BIP-I showed associations in the opposite direction. Depression and BIP-II had negative correlations with relative amplitude. All mood disorders were positively correlated with daytime sleepiness. Overall, we observed both genetic commonalities and differences across mood disorders in their relationships with biological rhythms: depression and BIP-I differed the most, while BIP-II was in an intermediate position.The present results suggest that the clinically observed associations between mood disorders and biological rhythms have shared genetic underpinnings. Future research considering possible joint mechanisms may offer potential avenues for improving disease detection and treatment.