Ni J, Zhou W, Cen H, Chen G, Huang J, Yin K, Sui C
Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230032, China.
Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Centre, Guangzhou, Guangdong 510060, China.
Osteoarthritis Cartilage. 2022 Mar;30(3):443-450. doi: 10.1016/j.joca.2021.11.021. Epub 2021 Dec 7.
To disentangle whether sleep disturbances have a causal effect on the risk of osteoarthritis (OA) using genetically based approaches.
We performed univariable and multivariable Mendelian randomization (MR) analyses using publicly released genome-wide association studies summary statistics to estimate the causal associations of sleep disturbances with OA risk. The inverse-variance weighted (IVW) method was utilized as primary MR analysis, whereas complementary methods including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) were applied to detect and correct for the presence of pleiotropy.
There were 228 independent instrumental variables (IVs) for insomnia and 78, 27 and 8 IVs for sleep duration, short sleep duration and long sleep duration, respectively. Univariable MR analysis suggested that genetically determined insomnia or short sleep duration exerted a causal effect on overall OA in an unfavorable manner (Insomnia: OR = 1.22, 95%CI = 1.15-1.30, P = 8.05 × 10; Short sleep duration: OR = 1.04, 95%CI = 1.02-1.07, P = 2.20 × 10). More compelling, increasing genetic liability to insomnia or short sleep duration was also associated with OA risk, after accounting for effects of insomnia or short sleep duration on body mass index, type 2 diabetes and depression individually, and in a combined model considering all three confounders.
Findings suggested consisted evidence for an adverse effect of increased insomnia or short sleep duration on OA risk. Strategies to mitigate sleep disturbances may be one of the cornerstones protects against OA.
采用基于基因的方法，剖析睡眠障碍是否对骨关节炎（OA）风险具有因果效应。
我们使用公开的全基因组关联研究汇总统计数据进行单变量和多变量孟德尔随机化（MR）分析，以估计睡眠障碍与OA风险之间的因果关联。采用逆方差加权（IVW）方法作为主要的MR分析，同时应用包括加权中位数、加权众数、MR-Egger回归以及MR多效性残差和异常值（MR-PRESSO）等补充方法来检测和校正多效性的存在。
失眠有228个独立工具变量（IVs），睡眠时长、短睡眠时长和长睡眠时长分别有78、27和8个IVs。单变量MR分析表明，基因决定的失眠或短睡眠时长对总体OA产生不利的因果效应（失眠：OR = 1.22，95%CI = 1.15 - 1.30，P = 8.05×10；短睡眠时长：OR = 1.04，95%CI = 1.02 - 1.07，P = 2.20×10）。更有说服力的是，在分别考虑失眠或短睡眠时长对体重指数、2型糖尿病和抑郁症的影响后，以及在考虑所有三个混杂因素的综合模型中，失眠或短睡眠时长的遗传易感性增加也与OA风险相关。
研究结果表明，有确凿证据支持失眠增加或短睡眠时长对OA风险有不利影响。减轻睡眠障碍可能是预防OA的基石之一。
