{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:39:40Z","timestamp":1791549580033,"version":"4.3.4"},"reference-count":48,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation","award":["82204067"],"award-info":[{"award-number":["82204067"]}]},{"name":"National Natural Science Foundation","award":["201920102401"],"award-info":[{"award-number":["201920102401"]}]},{"name":"Research on the Construction of a New Public Health Science System and Talent Training Model","award":["82204067"],"award-info":[{"award-number":["82204067"]}]},{"name":"Research on the Construction of a New Public Health Science System and Talent Training Model","award":["201920102401"],"award-info":[{"award-number":["201920102401"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: The causal connection between morning diurnal preference and psychiatric disorders remains enigmatic. Using bidirectional two-sample Mendelian randomization (MR), we aim to explore the potential causal associations between morning diurnal preference and seven prominent psychiatric disorders. Methods: MR is a genetic epidemiological method that leverages genetic variants as instrumental variables to infer causal associations between exposures and outcomes. We obtained morning diurnal preference data from genome-wide association study (GWAS) datasets and identified 252,287 individuals as morning people. Psychiatric disorder data were sourced from the FinnGen consortium R9 dataset. Our primary analysis used the inverse-variance weighted (IVW) approach to evaluate the overall causal effect by combining the estimates from each genetic variant. Addition analyses, including weighted median, MR-Egger regression, weighted mode, and simple mode techniques were conducted to ensure robustness. Results: Being a morning person is related to reduced odds of multiple psychiatric disorders, including depression or dysthymia (OR: 0.93, 95% CI: 0.88, 0.999), anxiety disorders (OR: 0.90, 95% CI: 0.84, 0.96), self-harming behaviors (OR: 0.87, 95% CI: 0.76, 0.99), substance-use disorders (OR: 0.81, 95% CI: 0.71, 0.93), alcohol dependence (OR: 0.82, 95% CI: 0.73, 0.92), alcohol use disorders (OR: 0.85, 95% CI: 0.76, 0.94), acute alcohol intoxication (OR: 0.86, 95% CI: 0.76, 0.96), schizophrenia (OR: 0.77, 95% CI: 0.65, 0.92), and schizophrenia or delusion (OR: 0.80, 95% CI: 0.70, 0.92). Alcohol dependence (OR: 0.97, 95% CI: 0.94, 0.999) and alcohol use disorders (OR: 0.96, 95% CI: 0.94, 0.99) were also related to a lower morning diurnal preference. Conclusions: Our study provides evidence that being a morning person is a protective factor for various psychiatric disorders from a genetic perspective. The results provide insights for potential targeted interventions to improve mental wellbeing.<\/jats:p>","DOI":"10.3390\/life14101225","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T16:16:37Z","timestamp":1727280997000},"page":"1225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring the Causal Association between Morning Diurnal Preference and Psychiatric Disorders: A Bidirectional Two-Sample Mendelian Randomization Analysis"],"prefix":"10.3390","volume":"14","author":[{"given":"Manman","family":"Chen","sequence":"first","affiliation":[{"name":"School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Din-Son","family":"Tan","sequence":"additional","affiliation":[{"name":"Vanke School of Public Health & Institute for Healthy China, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xijie","family":"Wang","sequence":"additional","affiliation":[{"name":"Vanke School of Public Health & Institute for Healthy China, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zichen","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1350-5273","authenticated-orcid":false,"given":"Zhilan","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daqian","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuankai","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"},{"name":"School of Health Policy and Management, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/S0140-6736(18)31612-X","article-title":"The Lancet Commission on Global Mental Health and Sustainable Development","volume":"392","author":"Patel","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"GBD 2019 Mental Disorders Collaborators (2022). Global, Regional, and National Burden of 12 Mental Disorders in 204 Countries and Territories, 1990\u20132019: A Systematic Analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry, 9, 137\u2013150.","DOI":"10.1016\/S2215-0366(21)00395-3"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101675","DOI":"10.1016\/j.eclinm.2022.101675","article-title":"Quantifying the Global Burden of Mental Disorders and Their Economic Value","volume":"54","author":"Arias","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.sleep.2021.07.011","article-title":"Circadian Disturbances, Sleep Difficulties and the COVID-19 Pandemic","volume":"91","author":"Salehinejad","year":"2022","journal-title":"Sleep. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e21864","DOI":"10.2196\/21864","article-title":"COVID-19, Social Isolation, and Mental Health Among Older Adults: A Digital Catch-22","volume":"23","author":"Cosco","year":"2021","journal-title":"J. Med. Internet Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41398-020-0694-0","article-title":"Circadian Rhythm Disruption and Mental Health","volume":"10","author":"Walker","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"zsab216","DOI":"10.1093\/sleep\/zsab216","article-title":"Evening-Types Show Highest Increase of Sleep and Mental Health Problems during the COVID-19 Pandemic\u2014Multinational Study on 19 267 Adults","volume":"45","author":"Merikanto","year":"2022","journal-title":"Sleep"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.sleep.2021.05.028","article-title":"Circadian Rhythm Abnormalities during the COVID-19 Outbreak Related to Mental Health in China: A Nationwide University-Based Survey","volume":"84","author":"Tao","year":"2021","journal-title":"Sleep Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e13442","DOI":"10.1111\/jsr.13442","article-title":"Mindful Larks and Lonely Owls: The Relationship between Chronotype, Mental Health, Sleep Quality, and Social Support in Young Adults","volume":"31","author":"Walsh","year":"2022","journal-title":"J. Sleep Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.aap.2011.09.021","article-title":"Sleep and Sleepiness during an Ultra Long-Range Flight Operation between the Middle East and United States","volume":"45","author":"Holmes","year":"2012","journal-title":"Accid. Anal. Prev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"204108","DOI":"10.1063\/5.0005077","article-title":"Siesta: Recent Developments and Applications","volume":"152","author":"Papior","year":"2020","journal-title":"J. Chem. Phys."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lopez-Minguez, J., Morosoli, J.J., Madrid, J.A., Garaulet, M., and Ordo\u00f1ana, J.R. (2017). Heritability of Siesta and Night-Time Sleep as Continuously Assessed by a Circadian-Related Integrated Measure. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-12460-x"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41467-018-08259-7","article-title":"Genome-Wide Association Analyses of Chronotype in 697,828 Individuals Provides Insights into Circadian Rhythms","volume":"10","author":"Jones","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6305","DOI":"10.1038\/s41380-021-01157-3","article-title":"Using Mendelian Randomisation Methods to Understand Whether Diurnal Preference Is Causally Related to Mental Health","volume":"26","author":"Casanova","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/s41398-022-02028-3","article-title":"The Hidden Link between Circadian Entropy and Mental Health Disorders","volume":"12","author":"Alachkar","year":"2022","journal-title":"Transl. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S2215-0366(18)30511-X","article-title":"Prevalence of Mental Disorders in China: A Cross-Sectional Epidemiological Study","volume":"6","author":"Huang","year":"2019","journal-title":"Lancet Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1093\/bioinformatics\/btw373","article-title":"PhenoScanner: A Database of Human Genotype-Phenotype Associations","volume":"32","author":"Staley","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4851","DOI":"10.1093\/bioinformatics\/btz469","article-title":"PhenoScanner V2: An Expanded Tool for Searching Human Genotype-Phenotype Associations","volume":"35","author":"Kamat","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1002\/sim.3034","article-title":"Mendelian Randomization: Using Genes as Instruments for Making Causal Inferences in Epidemiology","volume":"27","author":"Lawlor","year":"2008","journal-title":"Stat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/s41467-020-14389-8","article-title":"Physical Activity and Risks of Breast and Colorectal Cancer: A Mendelian Randomisation Analysis","volume":"11","author":"Papadimitriou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/ije\/dyr036","article-title":"Avoiding Bias from Weak Instruments in Mendelian Randomization Studies","volume":"40","author":"Burgess","year":"2011","journal-title":"Int. J. Epidemiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian Randomization with Invalid Instruments: Effect Estimation and Bias Detection through Egger Regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1093\/ije\/dyx102","article-title":"Robust Inference in Summary Data Mendelian Randomization via the Zero Modal Pleiotropy Assumption","volume":"46","author":"Hartwig","year":"2017","journal-title":"Int. J. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Xu, J., Zhang, S., Tian, Y., Si, H., Zeng, Y., Wu, Y., Liu, Y., Li, M., Sun, K., and Wu, L. (2022). Genetic Causal Association between Iron Status and Osteoarthritis: A Two-Sample Mendelian Randomization. Nutrients, 14.","DOI":"10.3390\/nu14183683"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hemani, G., Tilling, K., and Davey Smith, G. (2017). Orienting the Causal Relationship between Imprecisely Measured Traits Using GWAS Summary Data. PLoS Genet., 13.","DOI":"10.1101\/117101"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1002\/sim.7221","article-title":"A Framework for the Investigation of Pleiotropy in Two-sample Summary Data Mendelian Randomization","volume":"36","author":"Bowden","year":"2017","journal-title":"Stat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/EDE.0000000000000559","article-title":"Sensitivity Analyses for Robust Causal Inference from Mendelian Randomization Analyses with Multiple Genetic Variants","volume":"28","author":"Burgess","year":"2017","journal-title":"Epidemiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of Widespread Horizontal Pleiotropy in Causal Relationships Inferred from Mendelian Randomization between Complex Traits and Diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1093\/ije\/dyt179","article-title":"Calculating Statistical Power in Mendelian Randomization Studies","volume":"42","author":"Brion","year":"2013","journal-title":"Int. J. Epidemiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base Platform Supports Systematic Causal Inference across the Human Phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"eLife"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1001\/jamapsychiatry.2021.0959","article-title":"Genetically Proxied Diurnal Preference, Sleep Timing, and Risk of Major Depressive Disorder","volume":"78","author":"Daghlas","year":"2021","journal-title":"JAMA Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1080\/07420528.2020.1810063","article-title":"Associations between Diurnal Preference, Impulsivity and Substance Use in a Young-Adult Student Sample","volume":"38","author":"Evans","year":"2021","journal-title":"Chronobiol. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1111\/acer.14872","article-title":"Sleep and Circadian Differences between Light and Heavy Adult Alcohol Drinkers","volume":"46","author":"Burgess","year":"2022","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jad.2020.08.068","article-title":"Higher Prevalence of Intentional Self-Harm in Bipolar Disorder with Evening Chronotype: A Finding from the APPLE Cohort Study","volume":"277","author":"Esaki","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"114216","DOI":"10.1016\/j.bbr.2022.114216","article-title":"Circadian Rhythm Shifts and Alcohol Access in Adolescence Synergistically Increase Alcohol Preference and Intake in Adulthood in Male C57BL\/6 Mice","volume":"438","author":"Gonzalez","year":"2023","journal-title":"Behav. Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110","DOI":"10.5935\/1984-0063.20220003","article-title":"Association Analysis of Epworth Sleepiness Scale (ESS) Scores with Serotonin Transporter (5-HTT-LPR, 5-HTT-VNTR) and Circadian (PER3-VNTR) Genes","volume":"15","author":"Ozen","year":"2022","journal-title":"Sleep Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"113724","DOI":"10.1016\/j.bbr.2021.113724","article-title":"Antidepressant Actions of Melatonin and Melatonin Receptor Agonist: Focus on Pathophysiology and Treatment","volume":"420","author":"Wang","year":"2022","journal-title":"Behav. Brain Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s11011-019-00395-3","article-title":"Evidence for an Association of Serum Melatonin Concentrations with Recognition and Circadian Preferences in Patients with Schizophrenia","volume":"34","author":"Sahbaz","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/s41398-021-01464-x","article-title":"Melatonin\u2019s Neuroprotective Role in Mitochondria and Its Potential as a Biomarker in Aging, Cognition and Psychiatric Disorders","volume":"11","author":"Brown","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41386-022-01278-5","article-title":"Melatonergic Agents Influence the Sleep-Wake and Circadian Rhythms in Healthy and Psychiatric Participants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"47","author":"Moon","year":"2022","journal-title":"Neuropsychopharmacology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1126\/science.227056","article-title":"Phase Advance of the Circadian Sleep-Wake Cycle as an Antidepressant","volume":"206","author":"Wehr","year":"1979","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e12791","DOI":"10.1111\/jpi.12791","article-title":"Unanticipated Daytime Melatonin Secretion on a Simulated Night Shift Schedule Generates a Distinctive 24-h Melatonin Rhythm with Antiphasic Daytime and Nighttime Peaks","volume":"72","author":"Qian","year":"2022","journal-title":"J. Pineal Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"113835","DOI":"10.1016\/j.physbeh.2022.113835","article-title":"Night Shift Hormone: How Does Melatonin Affect Depression?","volume":"252","author":"Kholghi","year":"2022","journal-title":"Physiol. Behav."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s11920-022-01369-6","article-title":"Role of Melatonin in the Management of Sleep and Circadian Disorders in the Context of Psychiatric Illness","volume":"24","author":"Moon","year":"2022","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"113819","DOI":"10.1016\/j.psychres.2021.113819","article-title":"Effects of the COVID-19 Lockdown on Mental Health, Wellbeing, Sleep, and Alcohol Use in a UK Student Sample","volume":"298","author":"Evans","year":"2021","journal-title":"Psychiatry Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.1111\/ejn.14871","article-title":"Circadian Misalignment: A Biological Basis for Mood Vulnerability in Shift Work","volume":"52","author":"Chellappa","year":"2020","journal-title":"Eur. J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.5334\/jcr.193","article-title":"Diurnal Preference and Grey Matter Volume in a Large Population of Older Adults: Data from the UK Biobank","volume":"18","author":"Norbury","year":"2020","journal-title":"J. Circadian Rhythm."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/10\/1225\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:02:49Z","timestamp":1760112169000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/10\/1225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,25]]},"references-count":48,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["life14101225"],"URL":"https:\/\/doi.org\/10.3390\/life14101225","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,25]]}}}