睡眠特征与骨关节炎发病风险:两样本与多变量孟德尔随机化分析  

Sleep characteristics and risk of osteoarthritis:a two-sample and multivariate Mendelian randomization study

作　　者：陈继鑫 余伟杰 郭天赐 周沁心 牛朴钰 叶云天 刘爱峰[1,2] Chen Jixin;Yu Weijie;Guo Tianci;Zhou Qinxin;Niu Puyu;Ye Yuntian;Liu Aifeng(Department of Traumatology and Orthopedics,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300381,China;National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin 300381,China;Department of Traumatology and Orthopedics,Shaoxing Traditional Chinese Medicine Hospital,Shaoxing 312000,Zhejiang Province,China)

机构地区：[1]天津中医药大学第一附属医院骨伤科,天津市300381 [2]国家中医针灸临床医学研究中心,天津市300381 [3]绍兴市中医院骨伤科,浙江省绍兴市312000

出　　处：《中国组织工程研究》2024年第32期5203-5209,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81873316),项目负责人:刘爱峰;中华中医药学会骨病防治交叉研究项目(2023-GBJC-04),项目负责人:刘爱峰;天津市卫健委津门医学英才项目(TJSJMYXYC-D2-028),项目负责人:刘爱峰。

摘　　要：背景:近年来,流行病学研究显示睡眠特征是骨关节炎的危险因素,但睡眠特征与骨关节炎之间是否存在因果关联仍未知。目的:探讨7种睡眠表型与骨关节炎的因果关系,以期为临床防治提供理论依据。方法:从已发表的全基因组关联研究中选择了7个与睡眠相关的特征:睡眠持续时间、早上起床、白天小睡、早起/晚起类型、打鼾、失眠和嗜睡症,提取这些睡眠相关特征的工具变量。膝骨关节炎和髋骨关节炎的工具变量来自公开全基因组关联研究。通过双样本和多变量孟德尔随机化分析,以评估睡眠特征与结局风险的因果关系。采用逆方差加权法作为主要孟德尔随机化分析方法,采用加权中位数、加权模式、孟德尔随机化-Egger回归、孟德尔随机化多效性残差和异常值等方法检测和校正多效性的存在。结果与结论:①两样本孟德尔随机化的逆方差加权法结果显示,睡眠时间与膝骨关节炎发病风险呈负向因果关联(OR=0.621,95%CI:0.470-0.822,P=0.001),失眠与髋骨关节炎发病风险呈正向因果关联(OR=2.016,95%CI:1.249-3.254,P=0.005)。敏感性分析结果表明因果关系稳健,孟德尔随机化-Egger截距分析未检测到潜在的水平多效性(膝骨关节炎:P=0.468,髋骨关节炎:P=0.551)。②多变量孟德尔随机化结果显示,失眠与髋骨关节炎的因果关联没有统计学意义(P=0.715),睡眠时间对膝骨关节炎发病风险有直接的负向因果关联(OR=0.526,95%CI:0.336-0.824,P=0.005)。反向孟德尔随机化结果显示,膝骨关节炎不是睡眠时间的影响因素(P=0.757)。③睡眠时间与膝骨关节炎发病风险呈负相关,纠正短睡眠时间可能减轻膝骨关节炎发病风险。BACKGROUND:In recent years,epidemiological studies have shown that sleep patterns are risk factors for osteoarthritis,but the causal relationship between sleep characteristics and osteoarthritis remains unknown.OBJECTIVE:To investigate the causal relationship between seven sleep phenotypes and osteoarthritis,thereby providing a theoretical foundation for clinical prevention and intervention of osteoarthritis.METHODS:Seven sleep-related features,namely sleep duration,wake-up time,daytime napping,morning/evening preference,snoring,insomnia,and hypersomnia,were selected from published genome-wide association studies.Instrumental variables for these sleep-related features were extracted.Instrumental variables for knee osteoarthritis and hip osteoarthritis were obtained from publicly available genome-wide association studies.Causal relationships between sleep characteristics and outcome risks were evaluated using two-sample and multivariable Mendelian randomization analyses.The inverse variance weighted method was employed as the primary Mendelian randomization approach.Various methods,including weighted median,weighted mode,Mendelian randomization-Egger regression,Mendelian randomization pleiotropy-residual sum and outlier,were utilized to detect and correct for the presence of pleiotropy.RESULTS AND CONCLUSION:The results of the inverse variance-weighted method in the two-sample Mendelian randomization study revealed a detrimental causal association between the duration of sleep and the incidence risk of knee osteoarthritis[odds ratio(OR)=0.621,95%confidence interval(CI):0.470-0.822,P=0.001].Concurrently,insomnia displayed a positive causal connection with hip osteoarthritis risk(OR=2.016,95%CI:1.249-3.254,P=0.005).Sensitivity analysis affirmed the robustness of these causal relationships,and Mendelian randomization-Egger intercept analysis found no evidence of potential horizontal pleiotropy(knee osteoarthritis:P=0.468,hip osteoarthritis:P=0.551).Moreover,the results from the multivariable Mendelian randomization a

关 键 词：失眠 睡眠时间 骨关节炎 孟德尔随机化 因果关联 

分 类 号：R459.9[医药卫生—治疗学] R318.08[医药卫生—临床医学] R363