Sleep Patterns, Plasma Proteomic Signatures, and Risk of Major Brain Disorders: A Prospective Cohort Study
1
Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
Popul. Med. 2026;8(Supplement Supplement 1):A1304
ABSTRACT
INTRODUCTION:
Although individual sleep disturbances are associated with specific brain disorders, the overall impact of composite sleep patterns on multiple major brain disorders and the underlying biological mechanisms remains unclear.
METHODS:
Based on the UK Biobank prospective cohort, we included 402195 participants free of target diseases at baseline (42344 with plasma proteomics data). Four sleep dimensions (sleep duration, chronotype, insomnia, and daytime sleepiness) were assessed to construct a composite sleep score. Elastic net regression was employed to identify sleep-related proteins from 2911 plasma proteins. Cox proportional hazards models were applied to evaluate associations between sleep factors and incident major brain disorders (a composite endpoint including dementia, Parkinson’s disease, stroke, depression, anxiety disorders, and bipolar disorder). Mediation analysis was conducted to examine the mediating role of sleep-related proteomic signatures in these associations.
RESULTS:
Over a median follow-up of 14.38 years, 5646 incident cases of major brain disorders were recorded. All four healthy sleep factors and the composite sleep pattern were significantly associated with a reduced risk of brain disorders. A healthy sleep pattern was associated with a 19% lower risk (HR=0.810, 95% CI: 0.768–0.854, P<0.001). Among individual factors, the absence of daytime sleepiness showed the strongest protective effect (HR=0.716, 95% CI: 0.634–0.809, P<0.001). Proteomic analysis identified 187 duration-related, 245 chronotype-related, and 183 composite sleep pattern-related proteins. Mediation analysis revealed significant indirect effects through proteomic signatures, accounting for 10.1% (95% CI: 5.8%–14.4%) of the association for sleep duration, 29.3% (95% CI: 11.0%–47.6%) for chronotype, and 13.5% (95% CI: 8.4%–18.6%) for overall sleep pattern.
CONCLUSIONS:
Healthy sleep patterns represent protective factors against major brain disorders, with effects partially mediated by specific plasma proteomic signatures. These findings provide novel insights into the biological mechanisms linking sleep to brain health and suggest potential biomarkers for assessing disease risk.
Although individual sleep disturbances are associated with specific brain disorders, the overall impact of composite sleep patterns on multiple major brain disorders and the underlying biological mechanisms remains unclear.
METHODS:
Based on the UK Biobank prospective cohort, we included 402195 participants free of target diseases at baseline (42344 with plasma proteomics data). Four sleep dimensions (sleep duration, chronotype, insomnia, and daytime sleepiness) were assessed to construct a composite sleep score. Elastic net regression was employed to identify sleep-related proteins from 2911 plasma proteins. Cox proportional hazards models were applied to evaluate associations between sleep factors and incident major brain disorders (a composite endpoint including dementia, Parkinson’s disease, stroke, depression, anxiety disorders, and bipolar disorder). Mediation analysis was conducted to examine the mediating role of sleep-related proteomic signatures in these associations.
RESULTS:
Over a median follow-up of 14.38 years, 5646 incident cases of major brain disorders were recorded. All four healthy sleep factors and the composite sleep pattern were significantly associated with a reduced risk of brain disorders. A healthy sleep pattern was associated with a 19% lower risk (HR=0.810, 95% CI: 0.768–0.854, P<0.001). Among individual factors, the absence of daytime sleepiness showed the strongest protective effect (HR=0.716, 95% CI: 0.634–0.809, P<0.001). Proteomic analysis identified 187 duration-related, 245 chronotype-related, and 183 composite sleep pattern-related proteins. Mediation analysis revealed significant indirect effects through proteomic signatures, accounting for 10.1% (95% CI: 5.8%–14.4%) of the association for sleep duration, 29.3% (95% CI: 11.0%–47.6%) for chronotype, and 13.5% (95% CI: 8.4%–18.6%) for overall sleep pattern.
CONCLUSIONS:
Healthy sleep patterns represent protective factors against major brain disorders, with effects partially mediated by specific plasma proteomic signatures. These findings provide novel insights into the biological mechanisms linking sleep to brain health and suggest potential biomarkers for assessing disease risk.
| eISSN: | 2654-1459 |
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