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Associations between chronotype, morbidity and mortality in the UK Biobank cohort
Open accessAbstract
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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Sudlow, C., Gallacher, J., Allen, N., Beral, V., Burton, P., Danesh, J., Downey, P., Elliott, P., Green, J., Landray, M., et al. (2015) · PLOS Medicine · doi:10.1371/journal.pmed.1001779 · Cited by 12,728 · cited 1×
“We used data from the UK Biobank, a large, prospective, population-based cohort study that was designed to investigate risk factors for major disease of middle and older age (Sudlow et al. 2015).”
A self-assessment questionnaire to determine morningness- eveningness in human circadian rhythms
Home, J. K. (1976) · Medical Entomology and Zoology · Cited by 4,783
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Fry, A., Littlejohns, T. J., Sudlow, C., Doherty, N., Adamska, L., Sprosen, T., Collins, R., & Allen, N. E. (2017) · American Journal of Epidemiology · doi:10.1093/aje/kwx246 · Cited by 3,979 · cited 1×
“Finally, the UK Biobank cohort is generally healthier than the general UK population (Fry et al. 2017), and the degree to which these findings are generalisable to the entire population, or to other countries, is not known.”
BackgroundLife between Clocks: Daily Temporal Patterns of Human Chronotypes
Roenneberg, T., Wirz-Justice, A., & Merrow, M. (2003) · Journal of Biological Rhythms · doi:10.1177/0748730402239679 · Cited by 2,662 · cited 1×
“Circadian biologists mainly use two validated instruments used to assess either circadian preference, the MEQ (Horne and Östberg 1976), or circadian timing of behaviour, the Munich Chronotype Questionnaire (Roenneberg et al. 2003).”
Social Jetlag: Misalignment of Biological and Social Time
Wittmann, M., Dinich, J., Merrow, M., & Roenneberg, T. (2006) · Chronobiology International · doi:10.1080/07420520500545979 · Cited by 2,625 · cited 1×
“Evening types also commonly experience greater “social jetlag” (Wittmann et al. 2006), which is caused by going to bed and waking up later on non-work days compared to work days.”
Adverse metabolic and cardiovascular consequences of circadian misalignment
Scheer, F. A. J. L., Hilton, M. F., Mantzoros, C. S., & Shea, S. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808180106 · Cited by 2,351 · cited 2×
“Experimentally induced circadian misalignment has resulted in impairments in glucose metabolism (Scheer et al. 2009; Buxton et al. 2012; Leproult et al. 2014), profound disruption of rhythmic gene expression programmes (Archer et al. 2014) and impairments in mood (Boivin et al. 1997).”
Epidemiology of the human circadian clock
Roenneberg, T., Kuehnle, T., Juda, M., Kantermann, T., Allebrandt, K., Gordijn, M., & Merrow, M. (2007) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2007.07.005 · Cited by 1,545 · cited 2×
“Shorter sleep durations are more common in evening types (Roenneberg et al. 2007) and shorter sleep is associated with increased morbidity and mortality (Knutson 2010; Yin et al. 2017).”
Health and Deprivation: Inequality and the North
Townsend, P. D., Phillimore, P., & Beattie, A. (1987) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 1,473
Roenneberg, T., Allebrandt, K. V., Merrow, M., & Vetter, C. (2012) · Current Biology · doi:10.1016/j.cub.2012.03.038 · Cited by 1,407 · cited 2×
“Greater social jetlag has been associated with being overweight (BMI ≥25 kg/m²) (Roenneberg et al. 2012) and adverse cardiometabolic profiles (Rutters et al. 2014; Parsons et al. 2015).”
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Circadian disruption and human health
Fishbein, A. B., Knutson, K. L., & Zee, P. C. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148286 · Cited by 468
““Chronotype” refers to one’s preferred timing of sleep and activity, and evening chronotypes (“night owls”) are more likely to experience circadian disruption because of a mismatch between their internal clock and their social or professional responsibilities, and have increased risk of all-cause mortality compared wi…”
BackgroundSelf-citationImpact of Circadian Disruption on Cardiovascular Function and Disease
Chellappa, S. L., Vujović, N., Williams, J. S., & Scheer, F. A. J. L. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.07.008 · Cited by 346
“Chronotype (a measure of preferred timing of sleep and activity) may be linked to cardiovascular disease mortality, with evening types at higher risk [14].”
BackgroundCircadian disruption: what do we actually mean?
Vetter, C. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14255 · Cited by 333
Sleep Duration and Myocardial Infarction
Daghlas, I., Dashti, H. S., Lane, J. M., Aragam, K. G., Rutter, M. K., Saxena, R., & Vetter, C. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.07.022 · Cited by 289
“However, sleep is multidimensional (10), such that studies of both the independent and joint effects of sleep duration with other sleep traits such as sleep quality (11), sleep timing (12) , insomnia (13), and daytime napping (14) on cardiovascular outcomes are warranted.”
BackgroundValidation of the Sleep Regularity Index in Older Adults and Associations with Cardiometabolic Risk
Lunsford‐Avery, J. R., Engelhard, M., Návar, A. M., & Kollins, S. H. (2018) · Scientific Reports · doi:10.1038/s41598-018-32402-5 · Cited by 222
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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