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探讨偏头痛与静脉血栓栓塞症之间的双向关联:一项双向两样本 Mendelian Randomization 研究。

Exploring the Two-Way Link between Migraines and Venous Thromboembolism: A Bidirectional Two-Sample Mendelian Randomization Study.

机构信息

Vascular Surgery, Shandong Public Health Clinical Center, Shandong University, Jinan, China.

Department of Neurology, Shandong Public Health Clinical Center, Shandong University, Jinan, China.

出版信息

Thromb Haemost. 2024 Nov;124(11):1053-1060. doi: 10.1055/a-2313-0311. Epub 2024 Apr 24.

Abstract

BACKGROUND

The objective of this study is to utilize Mendelian randomization to scrutinize the mutual causality between migraine and venous thromboembolism (VTE) thereby addressing the heterogeneity and inconsistency that were observed in prior observational studies concerning the potential interrelation of the two conditions.

METHODS

Employing a bidirectional Mendelian randomization approach, the study explored the link between migraine and VTE, incorporating participants of European descent from a large-scale meta-analysis. An inverse-variance weighted (IVW) regression model, with random-effects, leveraging single nucleotide polymorphisms (SNPs) as instrumental variables was utilized to endorse the mutual causality between migraine and VTE. SNP heterogeneity was evaluated using Cochran's Q-test and to account for multiple testing, correction was implemented using the intercept of the MR-Egger method, and a leave-one-out analysis.

RESULTS

The IVW model unveiled a statistically considerable causal link between migraine and the development of VTE (odds ratio [OR] = 96.155, 95% confidence interval [CI]: 4.342-2129.458,  = 0.004), implying that migraine poses a strong risk factor for VTE development. Conversely, both IVW and simple model outcomes indicated that VTE poses as a weaker risk factor for migraine (IVW OR = 1.002, 95% CI: 1.000-1.004,  = 0.016). The MR-Egger regression analysis denoted absence of evidence for genetic pleiotropy among the SNPs while the durability of our Mendelian randomization results was vouched by the leave-one-out sensitivity analysis.

CONCLUSION

The findings of this Mendelian randomization assessment provide substantiation for a reciprocal causative association between migraine and VTE within the European population.

摘要

背景

本研究旨在利用孟德尔随机化方法仔细研究偏头痛与静脉血栓栓塞症(VTE)之间的相互因果关系,从而解决先前关于这两种情况潜在关联的观察性研究中观察到的异质性和不一致性问题。

方法

本研究采用双向孟德尔随机化方法,利用来自大规模荟萃分析的欧洲血统参与者,探讨偏头痛与 VTE 之间的联系。采用基于逆方差加权(IVW)回归模型,使用随机效应,利用单核苷酸多态性(SNP)作为工具变量,支持偏头痛与 VTE 之间的相互因果关系。使用 Cochran's Q 检验评估 SNP 异质性,并使用 MR-Egger 方法的截距进行多重检验校正,同时进行了一项剔除一个样本的分析。

结果

IVW 模型揭示了偏头痛与 VTE 发展之间存在统计学上显著的因果关系(优势比 [OR] = 96.155,95%置信区间 [CI]:4.342-2129.458,  = 0.004),表明偏头痛是 VTE 发展的一个强有力的危险因素。相反,IVW 和简单模型结果均表明 VTE 是偏头痛的一个较弱的危险因素(IVW OR = 1.002,95% CI:1.000-1.004,  = 0.016)。MR-Egger 回归分析表明,SNP 之间不存在遗传 pleiotropy 的证据,而剔除一个样本的敏感性分析则证实了我们的孟德尔随机化结果的稳健性。

结论

这项孟德尔随机化评估的结果为欧洲人群中偏头痛与 VTE 之间存在相互因果关系提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/070c/11518614/298cb97c683d/10-1055-a-2313-0311-i23060235-1.jpg

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