Knutson · Chronobiology international 2018 · Prospective cohort study · n=433268

Associations between chronotype, morbidity and mortality in the UK Biobank cohort.

Cited 274 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective non-randomized cohort study

PubMed 29642757 · doi:10.1080/07420528.2018.1454458 · record verified 2026-08-30

What was done

A prospective cohort study was conducted using data from 433,268 UK Biobank participants aged 38–73 followed for an average of 6.5 years. Chronotype was assessed via a single self-reported question categorizing individuals as definite morning, moderate morning, moderate evening, or definite evening types. Primary outcomes were all-cause mortality and cardiovascular disease (CVD) mortality, along with prevalence of comorbidities. Cox proportional hazards and logistic regression models adjusted for age, sex, ethnicity, smoking, BMI, sleep duration, socioeconomic status, and comorbidities.

What was found

Over follow-up, 10,534 deaths occurred, including 2,127 from CVD. Comparing definite evening to definite morning types, odds were significantly elevated for psychological disorders (OR 1.94, 95% CI 1.86–2.02, p < 0.001), 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). Definite evening types had an increased risk of all-cause mortality (HR 1.10, 95% CI 1.02–1.18, p = 0.012). Chronotype as an ordinal variable showed small increases in 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).

Why it matters

This is the first large prospective cohort linking evening chronotype with elevated all-cause mortality and higher comorbidity burden. It highlights circadian misalignment as a potential target for behavioral or workplace schedule interventions.

Limits

Chronotype was assessed via a single self-reported question rather than objective circadian measures or validated multi-item scales. The observational design cannot establish causality, residual confounding remains possible, and the follow-up duration (mean 6.5 years) was relatively short.

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