The causal associations of altered inflammatory proteins with sleep duration, insomnia and daytime sleepiness
The causal associations of altered inflammatory proteins with sleep duration, insomnia and daytime sleepiness
复制标题
DOI：
10.1093/sleep/zsad207
复制
发表时间：
2023-08-03
期刊：
影响因子：
5.6
通讯作者：
Yi，Minhan
中科院分区：
文献类型：
--
作者：
Zhang，Yuan;Zhao，Wangcheng;Yi，Minhan
研究目的越来越多的证据表明炎症与睡眠有关。本研究旨在评估睡眠特征包括失眠、白天过度嗜睡（EDS）和睡眠持续时间的关联和因果关系（短：<7小时;正常：7-9小时;长：≥9 h），C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）水平，方法应用标准的定量分析程序来估计比较组中每种蛋白的表达差异。然后，进行双样本孟德尔随机化（MR）分析，以探索其与已发表的全基因组关联研究汇总统计量的因果关系。逆方差加权被用来作为主要的方法，其次是几个互补的方法作为敏感性analysis.ResultsA共有44篇文章，51 879名参与者被列入定量分析。我们的研究结果显示，与对照组相比，失眠症患者的CRP、白细胞介素-1 β（IL-1β）、IL-6和TNF-α水平从0.36升高至0.58（标准化后），而EDS患者与对照组之间无显著差异。CRP和IL-6的表达与睡眠时间呈U/J型关系。在MR分析中，主要结果证明了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]）的因果效应。此外，发现IL-6与长睡眠时间相关（估计值：0.006; 95% CI，[0.000，0.013]）。这些结果是一致的敏感性analysis.ConclusionsThere高炎症档案失眠和极端的睡眠持续时间。同时，CRP和IL-6升高对睡眠时间延长有因果关系。进一步的研究可以集中在相关的上游和下游机制。
Study ObjectivesGrowing 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.MethodsStandard 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.ResultsA 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.ConclusionsThere 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.