The causal associations of altered inflammatory proteins with sleep duration, insomnia and daytime sleepiness

Yuan Zhang; Wangcheng Zhao; Kun Liu; Ziliang Chen; Quanming Fei; Namra Ahmad; Minhan Yi

doi:10.1093/sleep/zsad207

The causal associations of altered inflammatory proteins with sleep duration, insomnia and daytime sleepiness

Sleep. 2023 Oct 11;46(10):zsad207. doi: 10.1093/sleep/zsad207.

Authors

Yuan Zhang^{1

2}, Wangcheng Zhao^{1

2

3}, Kun Liu⁴, Ziliang Chen⁴, Quanming Fei^{1

2

3}, Namra Ahmad⁴, Minhan Yi^{1

4}

Affiliations

¹ Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
³ Xiangya School of Medicine, Central South University, Changsha, China.
⁴ School of Life Sciences, Central South University, Changsha, China.

PMID: 37535878
DOI: 10.1093/sleep/zsad207

Abstract

Study objectives: Growing evidence linked inflammation with sleep. This study aimed to evaluate the associations and causal effects of sleep traits including insomnia, excessive daytime sleepiness (EDS), and sleep duration (short: <7 h; normal: 7-9 h; long: ≥9 h), with levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukins.

Methods: Standard procedures of quantitative analysis were applied to estimate the expression differences for each protein in compared groups. Then, a two-sample Mendelian randomization (MR) analysis was performed to explore their causal relationships with published genome-wide association study summary statistics. The inverse-variance weighted was used as the primary method, followed by several complementary approaches as sensitivity analyses.

Results: A total of 44 publications with 51 879 participants were included in the quantitative analysis. Our results showed that the levels of CRP, interleukin-1β (IL-1β), IL-6, and TNF-α were higher from 0.36 to 0.58 (after standardization) in insomnia compared with controls, while there was no significant difference between participants with EDS and controls. Besides, there was a U/J-shaped expression of CRP and IL-6 with sleep durations. In MR analysis, the primary results demonstrated the causal effects of CRP on sleep duration (estimate: 0.017; 95% confidence intervals [CI], [0.003, 0.031]) and short sleep duration (estimate: -0.006; 95% CI, [-0.011, -0.001]). Also, IL-6 was found to be associated with long sleep duration (estimate: 0.006; 95% CI, [0.000, 0.013]). These results were consistent in sensitivity analyses.

Conclusions: There are high inflammatory profiles in insomnia and extremes of sleep duration. Meanwhile, elevated CRP and IL-6 have causal effects on longer sleep duration. Further studies can focus on related upstream and downstream mechanisms.

Keywords: CRP; IL-6; daytime sleepiness; inflammation; insomnia; sleep duration.

Abstract

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