Objective: This study aims to investigate the causal relationship between disruptions in sleep circadian rhythms and the risk of seven brain disorders.
Background: Disruptions in sleep circadian rhythms have been linked to an increased risk of dementia and mental health issues. However, the genetic-related causal evidence and underlying mechanisms connecting these disruptions to brain disorders remain unclear. Utilizing data from the UK Biobank, this study employs multivariate Cox-proportional hazards regression models, Mendelian randomization, and polygenic risk score (PRS) analysis to elucidate these relationships and identify potential intervention strategies.
Method: Sleep circadian rhythms, including shift work and sleep quality, were assessed using data from the UK Biobank. Multivariate Cox-proportional hazards regression models and Mendelian randomization were used to analyze the causal effects of disrupted circadian rhythms on seven brain disorders and their impact on brain structure. Sleep-related PRS was calculated to explore underlying mechanisms. Interactive analyses were conducted to identify at-risk populations and potential intervention points, such as physical frailty, physical activity, and CRP levels.
Results: Poor sleep quality was found to have a detrimental effect on brain disorders from both prospective and genetic perspectives. Shift work was specifically associated with an increased risk of stroke, dementia, and MDD. Brain regions, particularly the frontal lobe, were identified as being connected to sleep circadian rhythms. Interactive analyses revealed that physically frail individuals are at higher risk, with physical activity and CRP levels emerging as potential intervention points. PRS-based exploratory analyses suggested mediating effects of physical frailty and CRP in the associations between sleep quality and brain disorders.
Conclusion: This study provides evidence that disrupted sleep circadian rhythms negatively impact brain health and identifies potential mechanisms, at-risk populations, and intervention strategies. The findings highlight the importance of addressing sleep quality and shift work to mitigate the risk of brain disorders, offering new insights for preventive and therapeutic approaches.
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To cite this abstract in AMA style:
M. Zhong, J. Liu, Y. Li. Sleep Circadian Rhythms and Brain Disorders: A Large Prospective Cohort and Mendelian randomization Study [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/sleep-circadian-rhythms-and-brain-disorders-a-large-prospective-cohort-and-mendelian-randomization-study/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/sleep-circadian-rhythms-and-brain-disorders-a-large-prospective-cohort-and-mendelian-randomization-study/