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端粒长度与癫痫之间的因果关系:一项双向孟德尔随机化研究。

Causal relationship between telomere length and epilepsy: A bidirectional Mendelian randomization study.

机构信息

Jiangxi Provincial People's Hospital and The First Affiliated Hospital of Nanchang Medical College, Nanchang, China.

Beijing University of Chinese Medicine, Beijing, China.

出版信息

Epilepsia Open. 2023 Dec;8(4):1432-1439. doi: 10.1002/epi4.12817. Epub 2023 Aug 25.

Abstract

OBJECTIVE

Observational studies have suggested a link between telomere length (TL) and epilepsy, but the direction of the effect and whether it is causal or not is still being debated. The objective of this study was to investigate the causal relationship between TL and epilepsy using Mendelian randomization (MR) analysis.

METHODS

We performed a bidirectional two-sample MR analysis using pooled statistics from genome-wide association studies (GWAS) of TL and epilepsy. Additionally, we conducted a replication analysis using data from another GWAS study on epilepsy to validate our findings. The final results were analyzed using five MR methods, with the inverse-variance weighted (IVW) method as the primary outcome. We applied methods such as radial MR, MR pleiotropy residual and outlier test and MR Steiger filters to exclude outliers. Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy.

RESULTS

Our analysis found no evidence of a causal relationship between epilepsy and TL (all p-values >0.05). The sensitivity analysis confirms the robustness of these results.

SIGNIFICANCE

In summary, our study contradicts existing observational reports by not finding any evidence to support a causal relationship between epilepsy and TL. Further research is necessary to determine the underlying mechanism behind the association observed in observational studies.

摘要

目的

观察性研究表明端粒长度(TL)与癫痫之间存在关联,但效应的方向以及其是否具有因果关系仍存在争议。本研究旨在通过孟德尔随机化(MR)分析来研究 TL 与癫痫之间的因果关系。

方法

我们使用 TL 和癫痫的全基因组关联研究(GWAS)的汇总统计数据进行了双向两样本 MR 分析。此外,我们使用另一项癫痫 GWAS 研究的数据进行了复制分析,以验证我们的发现。最终结果使用五种 MR 方法进行分析,以逆方差加权(IVW)法作为主要结果。我们应用了径向 MR、MR 多效性残余和异常值检验以及 MR Steiger 过滤器等方法来排除异常值。还进行了敏感性分析以评估异质性和多效性。

结果

我们的分析没有发现癫痫与 TL 之间存在因果关系的证据(所有 p 值均>0.05)。敏感性分析证实了这些结果的稳健性。

意义

总之,我们的研究与现有的观察性报告相矛盾,没有发现任何证据支持癫痫与 TL 之间存在因果关系。需要进一步的研究来确定观察性研究中观察到的关联背后的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c38d/10690705/8191a2b7aed0/EPI4-8-1432-g002.jpg

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