Chinese Journal of Tissue Engineering Research ›› 2024, Vol. 28 ›› Issue (32): 5203-5209.doi: 10.12307/2024.509
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Chen Jixin1, 2, Yu Weijie1, 2, Guo Tianci1, 2, Zhou Qinxin3, Niu Puyu1, 2, Ye Yuntian1, 2, Liu Aifeng1, 2
Received:
2023-09-18
Accepted:
2023-10-20
Online:
2024-11-18
Published:
2023-12-29
Contact:
Liu Aifeng, Chief physician, Doctoral supervisor, 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; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China
About author:
Chen Jixin, MD candidate, 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
Supported by:
CLC Number:
Chen Jixin, Yu Weijie, Guo Tianci, Zhou Qinxin, Niu Puyu, Ye Yuntian, Liu Aifeng. Sleep characteristics and risk of osteoarthritis: a two-sample and multivariate Mendelian randomization study[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(32): 5203-5209.
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2.1 工具变量的选取 根据筛选标准,7个睡眠表型的工具变量被纳入研究。在该研究中,每个工具变量的 F 统计量均> 10,表明研究中存在弱工具变量偏倚的证据较低。 2.2 两样本MR研究 使用Cochran’s Q 检验检测工具变量的异质性,P > 0.05,可认为工具变量间不存在异质性,主要使用固定效应模型的 IVW 进行因果关系的探讨;反之,使用随机效应模型。根据表2所示的IVW结果,睡眠时间与膝骨关节炎发病存在负相关的因果关联,失眠与膝骨关节炎、髋骨关节炎发病存在正相关的因果关联,但失眠与膝骨关节炎的结果中,MR Egger和IVW总效应值的方向相反,故排除。其余睡眠表型未见因果关联。"
在失眠与髋骨关节炎的关联研究中,首先从失眠GWAS中提取42个显著相关水平(P < 5×10-8)和连锁不平衡(r2 < 0.001,10 000 kb)的SNP,与提取的髋骨关节炎数据集合并,并删除回文SNP共3个(rs2644128, rs2803296, rs8180817),检索PhenoScanner数据库,删除与身体质量指数相关6个SNP(rs10838708,rs11635495,rs2014830,rs2297787,rs4886860,rs56365214),MR-PRESSO 分析无离群值,SNP的F统计量为29.85-199.34。最终纳入33个SNP进行失眠与髋骨关节炎的MR分析,统计效能为1。5种统计方法结果相似,总效应值的方向一致,呈正相关,其中IVW和WME的统计学结果显著。MR Egger、WME、IVW、SM、WM的结果分别为(OR=3.086,95%CI:0.712-13.382,P=0.136)、(OR=1.957, 95%CI:1.034-3.702,P=0.004)、(OR=2.016,95%CI:1.249-3.254,P=0.005)、(OR=1.485,95%CI:0.378-5.825,P=0.090)、(OR=1.838,95%CI:0.742-4.556,P=0.019),结果表明失眠可能是髋骨关节炎发病的风险因素。随着失眠的次数增多,髋骨关节炎的发病风险随之增加,见图2A。 在睡眠时间与膝骨关节炎的关联研究中,首先从睡眠时间GWAS中提取71个显著相关水平(P < 5×10-8)和连锁不平衡(r2 < 0.001,10 000 kb)的SNP,与提取的膝骨关节炎数据集合并,并删除6个回文SNP(rs1972712,rs1611719,rs1517572,rs2236295,rs55658675,rs6889592),检索PhenoScanner数据库,删除与身体质量指数相关16个SNP(rs11039216,rs113021516,rs13107325,rs1463053,rs17732997,rs2186122,rs2192528,rs2279681,rs2279681,rs34556183,rs62444917,rs7016314,rs7115856,rs72771082,rs7831557,rs8047587),MR-PRESSO分析无离群值,SNP的F统计量为30.05-224.46。最终纳入49个SNP进行睡眠时间与膝骨关节炎的MR分析,统计效能为0.98。5种统计方法结果相似,总效应值的方向一致,呈正相关,其中IVW、WM和WME的统计学结果显著。MR Egger、WME、IVW、SM、WM的结果分别为(OR=0.435,95%CI:0.161-1.178, P=0.108)、(OR=0.534,95%CI:0.365-0.782,P=0.001)、(OR=0.621,95%CI:0.470-0.822,P=0.001)、(OR=0.427,95%CI:0.156-1.171,P=0.105)、(OR=0.445,95%CI:0.225-0.881,P=0.024),结果表明,睡眠持续时间可能是膝骨关节炎发病的保护因素。随着睡觉持续时间的减少,膝骨关节炎的发病风险随之增加,见图2B。"
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