颞下颌关节紊乱病与失眠之间因果关系的两样本孟德尔随机化研究

doi:10.7518/hxkq.2025.2024255

摘要/Abstract

摘要：

目的采用两样本孟德尔随机化（MR）的方法探讨颞下颌关节紊乱病（TMD）和失眠之间的关联。方法使用FinnGen数据库发布的全基因组关联研究统计数据进行TMD（n=377 277）及失眠（n=375 359）两个样本的双向MR分析。其中，TMD病例数10 303例和对照病例366 974例，失眠病例数4 214例和对照病例371 145例。使用双样本MR分析的R包，首先进行工具变量筛选，采用逆方差加权法（IVW）和MR-Egger作为主要的效果效应评估方法，加权中位数估计、加权模式和简单模式作为补充方法。采用IVW和MR-Egger法进行异质性检验；MR-Egger截距用于评估单核苷酸多态性（SNP）潜在水平多效性效应；进行敏感性分析，以确定潜在影响力的SNP。结果 MR分析显示TMD对失眠存在影响（OR=1.089，95%CI：1.017~1.166，P=0.014），而失眠对TMD不存在影响（OR=0.996，95%CI：0.964~1.029，P=0.816）。敏感性分析显示无异质性存在（P>0.05）；未发现水平多效性的存在（P>0.05）；没有任何单个SNP可能影响因果关系。所有研究结果表明，TMD与失眠之间的因果关系未受到任何个体SNP的显著影响，IV也不会对结果造成偏移。结论 MR分析结果显示TMD是失眠的风险因素，而失眠不是TMD的风险因素。

关键词: 颞下颌关节紊乱病, 失眠, 孟德尔随机化, 全基因组关联研究, 风险因素

Abstract:

Objective This study aimed to investigate the association between temporomandibular disorder (TMD) and insomnia using a two-sample Mendelian randomization (MR) approach. Methods Bidirectional MR analyses of two samples, TMD (n=377 277) and insomnia (n=375 359), were performed using genome-wide association study statistics published in the FinnGen database. Instrumental variables were first screened, and then inverse variance weighting (IVW) and MR-Egger were used as the main-effect assessment methods. Weighted median, weighted mode, and Simple mode served as supplementary methods. We used IVW and MR-Egger to test for heterogeneity, as well as MR-Egger intercepts to assess the single nucleotide polymorphism (SNP) potential level of multiplicity effects. Sensitivity analyses were conducted based on leave-one-out to identify potentially influential SNPs. All analyses were conducted using R (V.4.2.2) by using the two-sample MR R package and were considered statistically significant when P<0.05. Results MR analysis showed the presence of TMD on insomnia (OR=1.089, 95%CI: 1.017-1.166, P=0.014). Meanwhile, no effect of insomnia on TMD (OR=0.996, 95%CI: 0.964-1.029, P=0.816) was found. The sensitivity-analysis showed that no heterogeneity existed (P>0.05), and the presence of horizontal pleiotropy was not detected (P>0.05). Leave-one-out sensitivity analysis showed no single SNP, which may affect the causal relation. All findings indicated that the causal relationship between TMD and insomnia was not significantly affected by any individual SNP and that IV did not bias the results. Conclusion Results of MR analyses showed that TMD is a risk factor for insomnia, whereas insomnia is not a risk factor for TMD.

Key words: temporomandibular disorder, insomnia, Mendelian randomization, genome-wide association study, risk factors

中图分类号:

R782.6

袁玮, 程一茗, 崔蕴熠, 高朵朵. 颞下颌关节紊乱病与失眠之间因果关系的两样本孟德尔随机化研究[J]. 华西口腔医学杂志, 2025, 43(3): 354-361.

Yuan Wei, Cheng Yiming, Cui Yunyi, Gao Duoduo. A two-sample Mendelian randomization study on the association between temporomandibular disorder and insomnia[J]. West China Journal of Stomatology, 2025, 43(3): 354-361.

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结局	暴露	方法	OR值	95%CI	P值
TMD	失眠	IVW	0.996	0.964~1.029	0.816
		MR-Egger法	0.977	0.915~1.044	0.498
		加权中位数估计	1.021	0.975~1.069	0.374
		加权模式	1.020	0.905~1.149	0.744
		简单模式	1.018	0.910~1.139	0.755
失眠	TMD	IVW	1.089	1.017~1.166	0.014
		MR-Egger法	1.099	0.956~1.263	0.189
		加权中位数估计	1.074	0.974~1.184	0.152
		加权模式	1.031	0.795~1.337	0.818
		简单模式	1.016	0.756~1.366	0.916

暴露	结局	异质性				MR-Egger水平多效性
暴露	结局	Q值	df	I2	P值	PD截距	SE	P值
失眠	TMD	87.087	82	5.841%	0.330	0.003	0.005	0.517
TMD	失眠	97.313	100	2.761%	0.557	-0.001	0.007	0.888

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