Using Mendelian Randomisation methods to understand whether diurnal preference is causally related to mental health

Abstract

Late diurnal preference has been linked to poorer mental health outcomes, but the understanding of the causal role of diurnal preference on mental health and wellbeing is currently limited. Late diurnal preference is often associated with circadian misalignment (a mismatch between the timing of the endogenous circadian system and behavioural rhythms), so that evening people live more frequently against their internal clock. This study aims to quantify the causal contribution of diurnal preference on mental health outcomes, including anxiety, depression and general wellbeing and test the hypothesis that more misaligned individuals have poorer mental health and wellbeing using an actigraphy-based measure of circadian misalignment. Multiple Mendelian Randomisation (MR) approaches were used to test causal pathways between diurnal preference and seven well-validated mental health and wellbeing outcomes in up to 451,025 individuals. In addition, observational analyses tested the association between a novel, objective measure of behavioural misalignment (Composite Phase Deviation, CPD) and seven mental health and wellbeing outcomes. Using genetic instruments identified in the largest GWAS for diurnal preference, we provide robust evidence that early diurnal preference is protective for depression and improves wellbeing. For example, using one-sample MR, a twofold higher genetic liability of morningness was associated with lower odds of depressive symptoms (OR: 0.92, 95% CI: 0.88, 0.97). It is possible that behavioural factors including circadian misalignment may contribute in the chronotype depression relationship, but further work is needed to confirm these findings.

Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes

“…For example, recent work has suggested that there is a potentially genetic causal link between chronotype and odds of developing depressive symptoms [38] and similar findings have been reported for smoking [39] or alcohol abuse [40] and depression. In addition to smoking and alcohol intake, Neandertal DNA also showed significantly higher levels of association with pain and pain medications.…”

Neandertal introgression dissects the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes

“…Intriguingly, most of the enriched behavioral phenotypes closely resemble endophenotypes that are often strongly correlated with neuropsychiatric diseases, also on a genetic level. For example, recent work has suggested that there is a potentially genetic causal link between chronotype and odds of developing depressive symptoms (35) and similar findings have been reported for smoking (36) or alcohol abuse (37) and depression. In addition to smoking and alcohol intake, Neandertal DNA also showed significantly higher levels of association with pain and pain medications.…”

Recent advances in sleep and depression

“…higher social jetlag, lower relative amplitude of activity, and higher exposure to artificial light) with the MDD group, presenting identifiable and modifiable risk factors for depression [46]. Analyzing genetic and phenotypic data from a large sample of adults ( n = 451 025), O’Loughlin et al [47 ▪▪ ] found robust support for morning circadian preference as a protective factor against depression, as well as support for the role of circadian misalignment in the development of depression.…”