Using Mendelian Randomisation methods to understand whether diurnal preference is causally related to mental health
Open accessAbstract
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.
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Recent work has suggested a potentially genetic causal link between chronotype and odds of developing depressive symptoms, and similar findings have been reported for smoking or alcohol abuse and depression.
“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.”
From Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes (2022) · cites this paper as [38]
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- Authors
- O’Loughlin, J., Casanova, F., Jones, S. E., Hagenaars, S. P., Beaumont, R. N., Freathy, R. M., Watkins, E. R., Vetter, C., Rutter, M. K., Cain, S. W., Phillips, A. J. K., Windred, D. P., Wood, A. R., Weedon, M. N., & Tyrrell, J.
- Affiliations
- University of Exeter (GB)
- King's College London (GB)
- University of Colorado Boulder (US)
- Manchester Academic Health Science Centre (GB)
- Monash University (AU)
- Corresponding author
- Tyrrell, Jessica
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2021-06-08
- Volume
- 26
- Issue
- 11
- Pages
- 6305-6316
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC8760058
- OpenAlex
- W3169295369
- Cited by
- 44
- References
- 60
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 14 · 2023: 12 · 2022: 7 · 2021: 1
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Open Research Exeter (University of Exeter) (submittedVersion, cc-by)
- Funders
- Academy of Medical Sciences (SBF004\1079)
- Diabetes UK (17/0005700)
- RCUK | Medical Research Council (MR/S0151132)
- Wellcome Trust (WT104150)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- diurnal preference, chronotype, circadian misalignment, mental health, depression, anxiety, well-being, actigraphy, morningness, genetic instruments, causal inference
- MeSH terms
- Anxiety, Circadian Rhythm, Humans, Mental Health, Surveys and Questionnaires, Risk Factors, Sleep
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