Plasma Proteomic Landscape of Multidimensional Sleep Health and Its Association With Depression Risk Under Genetic Susceptibility

IF 2.7 2区医学 Q1 PSYCHIATRY

Depression and Anxiety Pub Date : 2026-10-09 DOI:10.1155/da/9191032

Feng Chen, Yanggang Hong, Yue Zhu, Yukai Wang, Qi Chen, Jiajun Li, Yangguang Lu, Haoxiong Guan, Huixiang Sheng, Ruijie Xie, Fan Ye

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Abstract

Background

Multidimensional sleep health, encompassing duration, snoring, chronotype, insomnia symptoms, and daytime sleepiness, is associated with various chronic diseases. However, its relationship with depression risk, especially the underlying molecular mechanisms across different levels of genetic susceptibility, remains unclear.

Methods

In this prospective cohort study, we analyzed data from 36,852 UK Biobank participants, integrating multidimensional sleep scores, plasma proteomic data covering 2,911 proteins, and polygenic risk scores (PRS) for depression. Sleep-related proteins were identified via elastic net regression, and their associations with incident depression were assessed using Cox proportional hazards models. Mediation and interaction analyses were conducted to explore the role of proteomic features and their effect modification by genetic risk.

Results

Seventy-three plasma proteins were selected by elastic net as sleep-related proteomic features, mainly involving immune regulation, neural signaling, metabolic homeostasis, and extracellular matrix remodeling. The proteomic score derived from these features was positively correlated with sleep health (r = 0.234, p < 1×10⁻¹⁰⁰). Healthy sleepers had a lower risk of depression (HR = 0.553, 95% CI: 0.454–0.674, p < 0.001), as did those with higher proteomic scores (HR = 0.660, 95% CI: 0.566–0.770, p < 0.001). Mediation analysis suggested that the proteomic signature statistically accounted for a modest proportion of the observed association between sleep health and incident depression. A significant additive interaction was observed between unhealthy sleep and high genetic risk (RERI = 0.280, 95% CI: 0.022–0.538).

Conclusion

This study characterizes the plasma proteomic profile of multidimensional sleep health and identifies sleep-associated proteomic signatures related to incident depression across levels of genetic susceptibility. These findings highlight potential biological pathways for further investigation and require independent replication and causal validation before clinical interpretation.

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在遗传易感性下，多维睡眠健康的血浆蛋白质组学景观及其与抑郁风险的关系

多维睡眠健康，包括持续时间、打鼾、睡眠类型、失眠症状和白天嗜睡，与各种慢性疾病有关。然而，其与抑郁症风险的关系，特别是不同水平遗传易感性的潜在分子机制，仍不清楚。在这项前瞻性队列研究中，我们分析了来自36852名英国生物银行参与者的数据，整合了多维睡眠评分、涵盖2911种蛋白质的血浆蛋白质组学数据和抑郁症的多基因风险评分（PRS）。通过弹性网络回归确定睡眠相关蛋白，并使用Cox比例风险模型评估其与事件抑郁症的关联。通过中介和相互作用分析来探讨遗传风险对蛋白质组学特征及其影响的影响。结果弹性网选择73种血浆蛋白作为睡眠相关的蛋白质组学特征，主要涉及免疫调节、神经信号、代谢稳态和细胞外基质重塑。由这些特征得出的蛋白质组学评分与睡眠健康呈正相关（r = 0.234, p < 1×10−100）。健康睡眠者患抑郁症的风险较低（HR = 0.553, 95% CI: 0.454-0.674, p < 0.001），蛋白质组学评分较高的人患抑郁症的风险也较低（HR = 0.660, 95% CI: 0.566-0.770, p < 0.001）。中介分析表明，在观察到的睡眠健康和抑郁症之间的关联中，蛋白质组学特征在统计上占了适度的比例。在不健康睡眠和高遗传风险之间观察到显著的加性相互作用（rei = 0.280, 95% CI: 0.022-0.538）。结论本研究表征了多维睡眠健康的血浆蛋白质组学特征，并在遗传易感性水平上确定了与抑郁症事件相关的睡眠相关蛋白质组学特征。这些发现强调了进一步研究的潜在生物学途径，在临床解释之前需要独立的复制和因果验证。

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来源期刊

Depression and Anxiety 医学-精神病学

CiteScore

15.00

自引率

1.40%

发文量

审稿时长

4-8 weeks

期刊介绍： Depression and Anxiety is a scientific journal that focuses on the study of mood and anxiety disorders, as well as related phenomena in humans. The journal is dedicated to publishing high-quality research and review articles that contribute to the understanding and treatment of these conditions. The journal places a particular emphasis on articles that contribute to the clinical evaluation and care of individuals affected by mood and anxiety disorders. It prioritizes the publication of treatment-related research and review papers, as well as those that present novel findings that can directly impact clinical practice. The journal's goal is to advance the field by disseminating knowledge that can lead to better diagnosis, treatment, and management of these disorders, ultimately improving the quality of life for those who suffer from them.