Zhang Yuan, Zhao Wangcheng, Liu Kun, Chen Ziliang, Fei Quanming, Ahmad Namra, Yi Minhan
Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Sleep. 2023 Oct 11;46(10). doi: 10.1093/sleep/zsad207.
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.
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.
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.
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.
越来越多的证据表明炎症与睡眠有关。本研究旨在评估包括失眠、日间过度嗜睡（EDS）和睡眠时间（短：<7小时；正常：7 - 9小时；长：≥9小时）等睡眠特征与C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）和白细胞介素水平之间的关联及因果效应。
采用定量分析的标准程序来估计比较组中每种蛋白质的表达差异。然后，进行两样本孟德尔随机化（MR）分析，以利用已发表的全基因组关联研究汇总统计数据来探索它们之间的因果关系。采用逆方差加权作为主要方法，随后采用几种补充方法进行敏感性分析。
定量分析共纳入44篇文献，51879名参与者。我们的结果显示，与对照组相比，失眠患者的CRP、白细胞介素-1β（IL-1β）、IL-6和TNF-α水平高出0.36至0.58（标准化后），而EDS患者与对照组之间无显著差异。此外，CRP和IL-6的表达与睡眠时间呈U/J形。在MR分析中，主要结果表明CRP对睡眠时间（估计值：0.017；95%置信区间[CI]，[0.003, 0.031]）和短睡眠时间（估计值：-0.006；95%CI，[-0.011, -0.001]）有因果效应。此外，发现IL-6与长睡眠时间有关（估计值：0.006；95%CI，[0.000, 0.013]）。这些结果在敏感性分析中是一致的。
失眠和睡眠时间极端情况下存在高炎症特征。同时，CRP和IL-6升高对较长睡眠时间有因果效应。进一步的研究可以关注相关的上游和下游机制。
