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Associations between chronotype, morbidity and mortality in the UK Biobank cohort
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Later chronotype (i.e. evening preference) and later timing of sleep have been associated with greater morbidity, including higher rates of metabolic dysfunction and cardiovascular disease (CVD). However, no one has examined whether chronotype is associated with mortality risk to date. Our objective was to test the hypothesis that being an evening type is associated with increased mortality in a large cohort study, the UK Biobank. Our analysis included 433 268 adults aged 38-73 at the time of enrolment and an average 6.5-year follow-up. The primary exposure was chronotype, as assessed through a single self-reported question-defining participants as definite morning types, moderate morning types, moderate evening types or definite evening types. The primary outcomes were all-cause mortality and mortality due to CVD. Prevalent disease was also compared among the chronotype groups. Analyses were adjusted for age, sex, ethnicity, smoking, body mass index, sleep duration, socioeconomic status and comorbidities. Greater eveningness, particularly being a definite evening type, was significantly associated with a higher prevalence of all comorbidities. Comparing definite evening type to definite morning type, the associations were strongest for psychological disorders (OR 1.94, 95% CI 1.86-2.02, p = < 0.001), followed by diabetes (OR 1.30, 95% CI 1.24-1.36, p = < 0.001), neurological disorders (OR 1.25, 95% CI 1.20-1.30, p = < 0.001), gastrointestinal/abdominal disorders (OR 1.23, 95% CI 1.19-1.27, p = < 0.001) and respiratory disorders (OR 1.22, 95% CI 1.18-1.26, p = < 0.001). The total number of deaths was 10 534, out of which 2127 were due to CVD. Greater eveningness, based on chronotype as an ordinal variable, was associated with a small increased risk of all-cause mortality (HR 1.02, 95% CI 1.004-1.05, p = 0.017) and CVD mortality (HR 1.04, 95% CI 1.00-1.09, p = 0.06). Compared to definite morning types, definite evening types had significantly increased risk of all-cause mortality (HR 1.10, 95% CI 1.02-1.18, p = 0.012). This first report of increased mortality in evening types is consistent with previous reports of increased levels of cardiometabolic risk factors in this group. Mortality risk in evening types may be due to behavioural, psychological and physiological risk factors, many of which may be attributable to chronic misalignment between internal physiological timing and externally imposed timing of work and social activities. These findings suggest the need for researching possible interventions aimed at either modifying circadian rhythms in individuals or at allowing evening types greater working hour flexibility.
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“Many human health effects are linked to the misalignment of chronotype (Knutson and von Schantz 2018), including cancer, obesity (Gyarmati et al. 2016; Papantoniou et al. 2016, 2017; Gan et al. 2018; Shi et al. 2020; Yousef et al. 2020), and diabetes (Gan et al. 2015; Larcher et al. 2015, 2016).”
From Archaic Introgression Shaped Human Circadian Traits (2023) · cites this paper as Knutson and von Schantz 2018
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Zhai, Z., Liu, X., Zhang, H., Dong, X., He, Y., Niu, M., Pan, M., Wang, C., Wang, X., & Li, Y. (2021) · BMC Public Health · doi:10.1186/s12889-021-10833-6 · Cited by 21
Chronotype, depression and hippocampal volume: cross-sectional associations from the UK Biobank
Norbury, R. (2019) · Chronobiology International · doi:10.1080/07420528.2019.1578229 · Cited by 22
Imbalanced sleep increases mortality risk by 14–34%: a meta-analysis
Ungvari, Z. I., Fekete, M., Varga, P., Fekete, J. T., Lehoczki, A., Buda, A., Szappanos, Á., Purebl, G., Ungvari, A., & Győrffy, B. (2025) · GeroScience · doi:10.1007/s11357-025-01592-y · Cited by 24
Circadian misalignment in obesity: The role for time-restricted feeding
Chambers, L., Seidler, K., & Barrow, M. (2023) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2023.07.086 · Cited by 20
Sirtoli, R., Mata, G. D. G., Rodrigues, R., Martínez‐Vizcaíno, V., López‐Gil, J. F., Guidoni, C. M., & Mesas, A. E. (2023) · Chronobiology International · doi:10.1080/07420528.2023.2256899 · Cited by 20
Chronotype in relation to shift work: A cohort study among 37,731 female nurses
de Bruijn, L., Berentzen, N. E., Vermeulen, R. C. H., Vlaanderen, J. J., Kromhout, H., van Leeuwen, F. E., & Schaapveld, M. (2024) · Journal of Sleep Research · doi:10.1111/jsr.14308 · Cited by 21
Influence of sleep on physiological systems in atherosclerosis
Kiss, M. G., Cohen, O., McAlpine, C. S., & Świrski, F. K. (2024) · Nature Cardiovascular Research · doi:10.1038/s44161-024-00560-7 · Cited by 24
Homocysteine, chronotype and clinical course in bipolar disorder patients
Ozdogan, M. G., Aydın, E. F., Üstündağ, M. F., Ceyhun, H. A., Oral, E., & Bakan, E. (2020) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2019.1710250 · Cited by 20
Lok, R., Weed, L., Winer, J. R., & Zeitzer, J. M. (2024) · Psychiatry Research · doi:10.1016/j.psychres.2024.115956 · Cited by 22
Ujma, P. P., Horváth, C. G., & Bódizs, R. (2023) · Scientific Reports · doi:10.1038/s41598-023-39011-x · Cited by 21
Archaic Introgression Shaped Human Circadian Traits
Velazquez-Arcelay, K., Colbran, L. L., McArthur, E., Brand, C. M., Rinker, D. C., Siemann, J. K., McMahon, D. G., & Capra, J. A. (2023) · Genome Biology and Evolution · doi:10.1093/gbe/evad203 · Cited by 18
“These results expand our understanding of how the genomes of humans and our closest relatives responded to environments with different light/dark cycles and demonstrate a coordinated contribution of admixture to human chronotype in a direction that is consistent with adaptation to higher latitudes.”
BackgroundResultNutritional entrainment of circadian rhythms under alignment and misalignment: A mechanistic review
Chambers, L., Seidler, K., & Barrow, M. (2022) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2022.06.010 · Cited by 18
Frescura, A., Lee, P. J., Soeta, Y., & Ariki, A. (2022) · Building and Environment · doi:10.1016/j.buildenv.2022.109405 · Cited by 18
Chronotype and mortality - a 37-year follow-up study in Finnish adults
Hublin, C., & Kaprio, J. A. (2023) · Chronobiology International · doi:10.1080/07420528.2023.2215342 · Cited by 18
Longitude-based time zone partitions and rates of suicide
Reis, D. J., Yen, P., Tizenberg, B., Gottipati, A., Postolache, S. Y., Riggs, D. D., Nance, M., Dagdag, A., Plater, L. Y., Federline, A., et al. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.07.080 · Cited by 19
An Overview of the Circadian Clock in the Frame of Chronotherapy: From Bench to Bedside
Vandenberghe, A., Lefranc, M., & Furlan, A. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14071424 · Cited by 18
Metadata
- Authors
- Knutson, K. L., & von Schantz, M.
- Affiliations
- Northwestern University (US)
- University of Surrey (GB)
- Corresponding author
- Knutson, Kristen L.
- Venue
- Chronobiology International
- Publisher
- Informa UK Limited
- Published
- 2018-04-11
- Volume
- 35
- Issue
- 8
- Pages
- 1-9
- ISSN
- 0742-0528 (ISSN-L)
- 1525-6073
- PMC
- PMC6119081
- OpenAlex
- W2789630154
- Cited by
- 275
- References
- 49
- Citations by year
- 2026: 21 · 2025: 36 · 2024: 40 · 2023: 38 · 2022: 32 · 2021: 39 · 2020: 32 · 2019: 26 · 2018: 11
- FWCI
- 35.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Chronobiology International (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Northumbria Research Link (Northumbria University) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Figshare (cc-by)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK095207)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- chronotype, eveningness, all-cause mortality, cardiovascular mortality, sleep timing, comorbidities, mental illness, diabetes mellitus, sleep duration, UK Biobank, circadian rhythm
- MeSH terms
- Noncommunicable Diseases, Activity Cycles, Adult, Aged, Cause of Death, Circadian Rhythm, Female, United Kingdom, Health Status, Humans, Life Expectancy, Male, Middle Aged, Personnel Staffing and Scheduling, Prognosis, Risk Factors, Social Behavior, Time Factors, Work Schedule Tolerance, Comorbidity, Prevalence, Risk Assessment
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