Yuan Wei, Cheng Yiming, Cui Yunyi, Gao Duoduo
Dept. of Prosthodontics, Handan Stomatological Hospital, Handan 056001, China.
Hebei Medical University, Shi-jiazhuang 050017, China.
Hua Xi Kou Qiang Yi Xue Za Zhi. 2025 Jun 1;43(3):354-361. doi: 10.7518/hxkq.2025.2024255.
This study aimed to investigate the association between temporomandibular disorder (TMD) and insomnia using a two-sample Mendelian randomization (MR) approach.
Bidirectional MR analyses of two samples, TMD (=377 277) and insomnia (=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 by using the two-sample MR R package and were considered statistically significant when <0.05.
MR analysis showed the presence of TMD on insomnia (OR=1.089, 95%CI: 1.017-1.166, =0.014). Meanwhile, no effect of insomnia on TMD (OR=0.996, 95%CI: 0.964-1.029, =0.816) was found. The sensitivity-analysis showed that no heterogeneity existed (>0.05), and the presence of horizontal pleiotropy was not detected (>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.
Results of MR analyses showed that TMD is a risk factor for insomnia, whereas insomnia is not a risk factor for TMD.
本研究旨在采用两样本孟德尔随机化(MR)方法探讨颞下颌关节紊乱病(TMD)与失眠之间的关联。
利用芬兰基因数据库中发表的全基因组关联研究统计数据,对两个样本(TMD=377277例,失眠=375359例)进行双向MR分析。首先筛选工具变量,然后采用逆方差加权(IVW)和MR-Egger作为主要效应评估方法。加权中位数、加权众数和简单众数作为补充方法。我们使用IVW和MR-Egger检验异质性,并使用MR-Egger截距评估单核苷酸多态性(SNP)潜在的多效性水平。基于逐一剔除法进行敏感性分析,以识别潜在的有影响的SNP。所有分析均使用两样本MR R包进行,当P<0.05时被认为具有统计学意义。
MR分析显示TMD对失眠有影响(比值比[OR]=1.089,95%置信区间[CI]:1.017-1.166,P=0.014)。同时,未发现失眠对TMD有影响(OR=0.996,95%CI:0.964-1.029,P=0.816)。敏感性分析显示不存在异质性(P>0.05),未检测到水平多效性的存在(P>0.05)。逐一剔除敏感性分析未发现可能影响因果关系的单个SNP。所有结果表明,TMD与失眠之间的因果关系不受任何单个SNP的显著影响,且工具变量未使结果产生偏差。
MR分析结果显示TMD是失眠的危险因素,而失眠不是TMD的危险因素。