Genetic liability for morning chronotype interacts with childhood trauma to predict depressive symptoms in women

INTRODUCTION: Depression is a highly heterogeneous disorder with a similarly heterogeneous neurobiological background. Understanding separate depressive phenotypes, driven by distinct aetiological pathways like early trauma and neurobiological contributors, can improve treatment. Furthermore, sex differences must be considered, as both the development and treatment of depression may be sex-specific. We aimed to investigate the sex-dependent association between polygenic risk for chronotypes, childhood traumas, and depression. METHODS: In a discovery sample of 273,033 participants GWASs were ran and polygenic risk scores (PRS) were calculated in a target sample of 25,476 participants, separately for morning and evening chronotypes. Effects of chronotype-PRS in interaction with childhood adversities were analysed. RESULTS: We identified 39 significant lead-SPNs (single nucleotide polymorphisms) and 44 genes associated with morning chronotype, and 69 significant lead-SNPs and 76 genes for evening chronotype. Heritability was comparable, at 12.1% for morning and 11.8% for evening chronotypes. No significant main effect of either chronotype-PRS was found on depressive symptom scores, however, in interaction with childhood traumas, morningness-PRS showed a significant effect on depressive symptom scores in women. DISCUSSION: Our findings highlight important sex differences in the aetiological role of known risk factors for depression, such as chronotype or early trauma, and may have implications in the prevention of mood disorders in those genetically vulnerable and exposed to early risk factors.