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[一项关于失眠与骨质疏松症关系的孟德尔随机化研究]

[A Mendelian randomization study on the relationship between insomnia and osteoporosis].

作者信息

Liu H Z, Fu X M, Li X J, Wang Y H, Hu X D, Xu H J, Wang A N, Lyu Z H, Dong S, Pei Y

机构信息

Department of Endocrinology, Aerospace Center Hospital, Beijing 100049, China.

Clinics of Cadre, Department of Outpatient, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2024 Aug 1;63(8):776-780. doi: 10.3760/cma.j.cn112138-20240207-00105.

DOI:10.3760/cma.j.cn112138-20240207-00105
PMID:39069866
Abstract

To explore the relationship between insomnia and osteoporosis. Mendelian randomization (MR) analysis were used in this study. The single nucleotide polymorphisms (SNPs) related to insomnia from genome-wide association analysis research data were selected as the instrumental variables by using inverse variance weighted (IVW), MR-Egger regression, weighted median method, maximum likelihood, penalized weighted median estimator, and Mendelian randomization robust adjusted profile score (MR-RAPS) to determine the causal relationship between insomnia and osteoporosis. Odds ratio () and 95% confidence interval () values were used to evaluate the association between insomnia and osteoporosis. Cochran's -test was used to detect heterogeneity of SNPs, MR-Egger regression was used to test for level pleiotropy, and the leave-one-out method was used to test sensitivity, MR pleiotropy residual sum and outlier (MR-PRESSO) method and radial MR were used to detect erroneous outliers. The screening criteria were set based on the three major assumptions of MR; finally, 31 SNPs were included in the MR analysis. The results of MR causal effect analysis using the IVW method showed that insomnia increased the risk of osteoporosis by about 0.7% (=1.007, 95% 1.001-1.014, =0.044); heterogeneity testing showed heterogeneity between SNPs (=57.91, <0.001); and the MR- Egger intercept test did not indicate horizontal pleiotropy in this study (intercept value=3.807×10, =0.888). Leave-one-out method showed that no single SNP had a significant impact on the overall results. No abnormal SNP was detected according to the MR-PRESSO results (=0.059), and radial MR did not detect any outliers. Mendelian randomization analysis showed that insomnia can increase the risk of osteoporosis.

摘要

为探究失眠与骨质疏松症之间的关系。本研究采用孟德尔随机化(MR)分析。利用逆方差加权(IVW)、MR-Egger回归、加权中位数法、最大似然法、惩罚加权中位数估计法和孟德尔随机化稳健调整轮廓评分(MR-RAPS),从全基因组关联分析研究数据中选择与失眠相关的单核苷酸多态性(SNP)作为工具变量,以确定失眠与骨质疏松症之间的因果关系。采用比值比(OR)和95%置信区间(CI)值评估失眠与骨质疏松症之间的关联。使用 Cochr an's Q检验检测SNP的异质性,采用MR-Egger回归检验水平多效性,并使用留一法检验敏感性,采用MR多效性残差和异常值(MR-PRESSO)方法以及径向MR检测错误的异常值。基于MR的三个主要假设设定筛选标准;最终,31个SNP被纳入MR分析。使用IVW方法进行MR因果效应分析的结果显示,失眠使骨质疏松症风险增加约0.7%(OR=1.007,95%CI 1.001-1.014,P=0.044);异质性检验显示SNP之间存在异质性(Q=57.91,P<0.001);并且本研究中的MR-Egger截距检验未表明存在水平多效性(截距值=3.807×10,P=0.888)。留一法显示,没有单个SNP对总体结果有显著影响。根据MR-PRESSO结果未检测到异常SNP(P=0.059),径向MR也未检测到任何异常值。孟德尔随机化分析表明,失眠会增加患骨质疏松症的风险。

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