Chronotype, Genetic Risk, Lifestyle, and Risk of Depression and Anxiety: A Prospective Cohort Study

Abstract

We aimed to evaluate associations of chronotype, genetic risk, and lifestyle with depression and anxiety. A total of 242,391 participants without anxiety and depression at baseline in UK Biobank were included. During a total of 3,393,260.1 and 1,371,872.8 person-years follow-up, we found 11,824 (4.88%) incident depression and 10,051 (4.15%) incident anxiety cases, respectively. Compared with definite morning group, individuals with intermediate (HR = 1.09, 95% CI = 1.04‒1.13) and definite evening chronotype (HR = 1.45, 95% CI = 1.36‒1.55) have higher risks of depression, and individuals with definite evening chronotype (HR = 1.27, 95% CI = 1.18‒1.37) have a higher risk of anxiety. We found joint association between chronotype and genetic risk, those with high genetic risk and definite evening chronotype had the highest risk of depression (HR = 2.01, 95% CI = 1.81‒2.23) and anxiety (HR = 1.40, 95% CI = 1.24‒1.58). We also found joint association between chronotype and lifestyle, those with least healthy lifestyle and definite evening chronotype had the highest risk of depression (HR = 1.99, 95% CI = 1.65‒2.40) and anxiety (HR = 1.69, 95% CI = 1.36‒2.10). Individuals with evening chronotype are associated with higher risks of depression and anxiety.

Keywords

anxiety / chronotype / depression / genetic risk / lifestyle

References

[1] Q. S. Mao, Y. X. Guo, X. L. Tian, H. L. Zhao, and Y. Z. Kong, “Global Burden of Mental Disorders in 204 Countries and Territories Results From the Global Burden of Disease Study 2021,” World Journal of Psychiatry 15, no. 8 (2025): 106887.

[2] GBD 2019 Mental Disorders Collaborators. Global, Regional, and National Burden of 12 Mental Disorders in 204 Countries and Territories, 1990–2019: A Systematic Analysis for the Global Burden of Disease Study 2019. The Lancet Psychiatry 9, no. 2 (2022): 137–150.

[3] GBD 2021 Diseases and Injuries Collaborators. Global Incidence, Prevalence, Years Lived with Disability (YLDs), Disability-Adjusted Life-Years (DALYs), and Healthy Life Expectancy (HALE) for 371 Diseases and Injuries in 204 Countries and Territories and 811 Subnational Locations, 1990–2021: A Systematic Analysis for the Global Burden of Disease Study 2021. Lancet (London, England) 403, no. 10440 (2024): 2133–2161.

[4] GBD 2021 Causes of Death Collaborators. Global Burden of 288 Causes of Death and Life Expectancy Decomposition in 204 Countries and Territories and 811 Subnational Locations, 1990–2021: A Systematic Analysis for the Global Burden of Disease Study 2021. Lancet (London, England) 403, no. 10440 (2024): 2100–2132.

[5] L. Barrea, L. Verde, C. Vetrani, et al., “Evening Chronotype is Associated With Hormonal and Metabolic Disorders in Polycystic Ovary Syndrome,” Journal of Pineal Research 74, no. 2 (2023): e12844.

[6] S. Kianersi, Y. Liu, M. Guasch-Ferré, et al., “Unhealthy Lifestyle, and Diabetes Risk in Middle-Aged U.S. Women:A Prospective Cohort Study,” Annals of Internal Medicine> 176, no. 10 (2023): 1330–1339.

[7] T. Partonen, “Extreme Chronotype, Regardless of Misalignment, Links to Cardiovascular Disease Risks,” Sleep 46, no. 6 (2023): zsad081.

[8] G. Muscogiuri, L. Barrea, S. Aprano, et al., “Chronotype and Adherence to the Mediterranean Diet in Obesity: Results From the Opera Prevention Project,” Nutrients 12, no. 5 (2020): 1354.

[9] S. Bauducco, C. Richardson, and M. Gradisar, “Chronotype, Circadian Rhythms and Mood,” Current Opinion Psychology 34 (2020): 77–83.

[10] M. M. Zhang, Y. Ma, L. T. Du, et al., “Sleep Disorders and Non-Sleep Circadian Disorders Predict Depression: A Systematic Review and Meta-Analysis of Longitudinal Studies,” Neuroscience and Biobehavioral Reviews 134 (2022): 104532.

[11] H. Zou, H. Zhou, R. Yan, Z. Yao, and Q. Lu, “Chronotype, Circadian Rhythm, and Psychiatric Disorders: Recent Evidence and Potential Mechanisms,” Frontiers in Neuroscience 16 (2022): 811771.

[12] B. J. Coombes, I. Landi, K. W. Choi, et al., “The Genetic Contribution to the Comorbidity of Depression and Anxiety: A Multi-Site Electronic Health Records Study of Almost 178 000 People,” Psychological Medicine 53, no. 15 (2023): 7368–7374.

[13] K. S. Kendler, H. Ohlsson, J. Sundquist, and K. Sundquist, “Risk for Mood, Anxiety, and Psychotic Disorders in Individuals at High and Low Genetic Liability for Bipolar Disorder and Major Depression,” JAMA Psychiatry 79, no. 11 (2022): 1102–1109.

[14] J. Firth, M. Solmi, R. E. Wootton, et al., “A Meta-Review of “Lifestyle Psychiatry”: The Role of Exercise, Smoking, Diet and Sleep in the Prevention and Treatment of Mental Disorders,” World Psychiatry: Official Journal of the World Psychiatric Association (WPA) 19, no. 3 (2020): 360–380.

[15] D. Vancampfort, J. Firth, B. Stubbs, et al., “The Efficacy, Mechanisms and Implementation of Physical Activity as an Adjunctive Treatment in Mental Disorders: A Meta-Review of Outcomes, Neurobiology and Key Determinants,” World Psychiatry: Official Journal of the World Psychiatric Association (WPA) 24, no. 2 (2025): 227–239.

[16] S. J. M. Druiven, J. H. M. Hovenkamp-Hermelink, S. E. Knapen, et al., “Stability of Chronotype Over a 7-Year Follow-Up Period and its Association with Severity of Depressive and Anxiety Symptoms,” Depression and Anxiety 37, no. 5 (2020): 466–474.

[17] S. J. M. Druiven, S. E. Knapen, B. Penninx, et al., “Can Chronotype Function as Predictor of a Persistent Course of Depressive and Anxiety Disorder?,” Journal of Affective Disorders 242 (2019): 159–164.

[18] C. Vetter, S. C. Chang, E. E. Devore, F. Rohrer, O. I. Okereke, and E. S. Schernhammer, “Prospective Study of Chronotype and Incident Depression Among Middle- and Older-Aged Women in the Nurses' Health Study II,” Journal of Psychiatric Research 103 (2018): 156–160.

[19] B. P. Hasler, “Chronotype and Mental Health: Timing Seems to Matter, but How, Why, and for Whom?,” World Psychiatry: Official Journal of the World Psychiatric Association (WPA) 22, no. 2 (2023): 329–330.

[20] S. Basnet, I. Merikanto, T. Lahti, et al., “Associations of Common Noncommunicable Medical Conditions and Chronic Diseases with Chronotype in a Population-Based Health Examination Study,” Chronobiology International 34, no. 4 (2017): 462–470.

[21] H. Konttinen, E. Kronholm, T. Partonen, N. Kanerva, S. Männistö, and A. Haukkala, “Morningness‒Eveningness, Depressive Symptoms, and Emotional Eating: A Population-Based Study,” Chronobiology International 31, no. 4 (2014): 554–563.

[22] I. Merikanto, E. Kronholm, M. Peltonen, T. Laatikainen, E. Vartiainen, and T. Partonen, “Circadian Preference Links to Depression in General Adult Population,” Journal of Affective Disorders 188 (2015): 143–148.

[23] M. Maukonen, A. S. Havulinna, S. Männistö, N. Kanerva, V. Salomaa, and T. Partonen, “Genetic Associations of Chronotype in the Finnish General Population,” Journal of Biological Rhythms 35, no. 5 (2020): 501–511.

[24] M. Maukonen, N. Kanerva, T. Partonen, et al., “The Associations Between Chronotype, a Healthy Diet and Obesity,” Chronobiology International 33, no. 8 (2016): 972–981.

[25] B. P. Hasler, M. L. Wallace, J. L. Graves, B. S. G. Molina, and S. L. Pedersen, “Circadian Preference is Associated With Multiple Domains of Trait and State Level Impulsivity,” Chronobiology International 39, no. 6 (2022): 792–804.

[26] R. Tavernier, M. Munroe, and T. Willoughby, “Perceived Morningness‒Eveningness Predicts Academic Adjustment and Substance Use Across University, but Social Jetlag is Not to Blame,” Chronobiology International 32, no. 9 (2015): 1233–1245.

[27] R. W. Logan and C. A. McClung, “Rhythms of Life: Circadian Disruption and Brain Disorders Across the Lifespan,” Nature Reviews Neuroscience 20, no. 1 (2019): 49–65.

[28] C. S. Colwell, “Linking Neural Activity and Molecular Oscillations in the SCN,” Nature Reviews Neuroscience 12, no. 10 (2011): 553–569.

[29] A. L. Baird, A. N. Coogan, A. Siddiqui, R. M. Donev, and J. Thome, “Adult Attention-Deficit Hyperactivity Disorder is Associated with Alterations in Circadian Rhythms at the Behavioural, Endocrine and Molecular Levels,” Molecular Psychiatry 17, no. 10 (2012): 988–995.

[30] A. N. Coogan and N. M. McGowan, “A Systematic Review of Circadian Function, Chronotype and Chronotherapy in Attention Deficit Hyperactivity Disorder,” Attention Deficit Hyperactivity Disorder 9, no. 3 (2017): 129–147.

[31] E. A. Winiger, J. M. Ellingson, C. L. Morrison, et al., “Sleep Deficits and Cannabis Use Behaviors: An Analysis of Shared Genetics Using Linkage Disequilibrium Score Regression and Polygenic Risk Prediction,” Sleep 44, no. 3 (2021): zsaa188.

[32] N. Arora, R. C. Richmond, B. M. Brumpton, et al., “Self-Reported Insomnia Symptoms, Sleep Duration, Chronotype and the Risk of Acute Myocardial Infarction (AMI): A Prospective Study in the UK Biobank and the HUNT Study,” European Journal of Epidemiology 38, no. 6 (2023): 643–656.

[33] H. Xie, Z. Xi, S. Wen, et al., “Associations Between Chronotype, Genetic Susceptibility and Risk of Colorectal Cancer in UK Biobank,” Journal of Epidemiology and Global Health 15, no. 1 (2025): 57.

[34] C. Sudlow, J. Gallacher, N. Allen, et al., “UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age,” PLoS Medicine 12, no. 3 (2015): e1001779.

[35] M. Xu, X. Yin, and Y. Gong, “Lifestyle Factors in the Association of Shift Work and Depression and Anxiety,” JAMA Network Open 6, no. 8 (2023): e2328798.

[36] X. Han, C. Hou, H. Yang, et al., “Disease Trajectories and Mortality Among Individuals Diagnosed with Depression: A Community-Based Cohort Study in UK Biobank,” Molecular Psychiatry 26, no. 11 (2021): 6736–6746.

[37] C. Bycroft, C. Freeman, D. Petkova, et al., “The UK Biobank Resource With Deep Phenotyping and Genomic Data,” Nature 562, no. 7726 (2018): 203–209.

[38] X. Hao, Z. Shao, N. Zhang, et al., “Integrative Genome-Wide Analyses Identify Novel Loci Associated with Kidney Stones and Provide Insights Into its Genetic Architecture,” Nature Communications 14, no. 1 (2023): 7498.

[39] C. C. Chang, C. C. Chow, L. C. Tellier, S. Vattikuti, S. M. Purcell, and J. J. Lee, “Second-Generation PLINK: Rising to the Challenge of Larger and Richer Datasets,” GigaScience 4 (2015): 7.

[40] Z. Shao, W. Tang, H. Wu, Y. Kong, and X. Hao, “Incorporating Multiple Functional Annotations to Improve Polygenic Risk Prediction Accuracy,” Cell Genomics 5, no. 6 (2025): 100850.

[41] T. Ge, C. Y. Chen, Y. Ni, Y. A. Feng, and J. W. Smoller, “Polygenic Prediction via Bayesian Regression and Continuous Shrinkage Priors,” Nature Communications 10, no. 1 (2019): 1776.

[42] N. R. Wray, S. Ripke, M. Mattheisen, et al., “Genome-Wide Association Analyses Identify 44 Risk Variants and Refine the Genetic Architecture of Major Depression,” Nature Genetics 50, no. 5 (2018): 668–681.

[43] T. Otowa, K. Hek, M. Lee, et al., “Meta-Analysis of Genome-Wide Association Studies of Anxiety Disorders,” Molecular Psychiatry 21, no. 10 (2016): 1391–1399.

[44] H. M. E. Foster, C. A. Celis-Morales, B. I. Nicholl, et al., “The Effect of Socioeconomic Deprivation on the Association between an Extended Measurement of Unhealthy Lifestyle Factors and Health Outcomes: A Prospective Analysis of the UK Biobank Cohort,” The Lancet Public Health 3, no. 12 (2018): e576–e585.

[45] D. Li, J. Xie, L. Wang, Y. Sun, Y. Hu, and Y. Tian, “Genetic Susceptibility and Lifestyle Modify the Association of Long-Term Air Pollution Exposure on Major Depressive Disorder: A Prospective Study in UK Biobank,” BMC Medicine [Electronic Resource] 21, no. 1 (2023): 67.

[46] P. W. G. Tennant, E. J. Murray, K. F. Arnold, et al., “Use of Directed Acyclic Graphs (DAGs) to Identify Confounders in Applied Health Research: Review and Recommendations,” International Journal of Epidemiology 50, no. 2 (2021): 620–632.

[47] C. Vetter, H. S. Dashti, J. M. Lane, et al., “Night Shift Work, Genetic Risk, and Type 2 Diabetes in the UK Biobank,” Diabetes Care 41, no. 4 (2018): 762–769.

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