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孟德尔随机化分析结合荟萃分析的证据,用于因果验证35种血液和尿液代谢物与腰椎间盘突出症之间的关系。

Evidence from Mendelian randomization analysis combined with meta-analysis for the causal validation of the relationship between 35 blood and urine metabolites and lumbar disc herniation.

作者信息

Yang Jingze, Xu Wanxian, Chen Daolei, Yang Haiqing, Zhou Zhaowen

机构信息

Department of Orthopaedics, First People's Hospital of Kunming City & Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

出版信息

Medicine (Baltimore). 2025 Jun 20;104(25):e42749. doi: 10.1097/MD.0000000000042749.

DOI:10.1097/MD.0000000000042749
PMID:40550047
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12187337/
Abstract

Lumbar disc herniation (LDH) is a prevalent condition affecting the spine. In recent years, a growing body of observational research has explored the influence of metabolites found in blood and urine on the development of LDH. By applying Mendelian randomization techniques to these metabolic markers, it becomes possible to uncover potential causal links with LDH, offering novel perspectives for its prevention and therapeutic intervention. This research employed a two-sample Mendelian randomization (MR) approach to explore the association between 35 metabolites found in blood and urine and the occurrence of LDH, utilizing datasets from 2 independent sources. The most notable findings from the MR analysis, particularly those obtained through the inverse variance weighted method, were further evaluated via meta-analysis. To enhance result reliability, multiple correction methods were applied to adjust the significance thresholds. Lastly, a reverse MR analysis was carried out to confirm the directional causal influence of the selected metabolites on LDH. MR analysis was performed to investigate the relationship between 35 blood and urine metabolites and LDH using data from the Finngen R10 and UK Biobank databases. The most significant results from both sets of MR analyses, derived using the inverse variance weighted method, were then subjected to a meta-analysis. Multiple corrections were applied to the significance thresholds in the meta-analysis, resulting in an odds ratio of 0.860 (95% confidence interval: 0.795-0.930, P = .0052). Additionally, the identified positive metabolites did not exhibit reverse causality with LDH in either dataset. Apolipoprotein acts as a protective factor against LDH, potentially reducing the risk of developing the condition and slowing its progression.

摘要

腰椎间盘突出症(LDH)是一种常见的脊柱疾病。近年来,越来越多的观察性研究探讨了血液和尿液中发现的代谢物对LDH发生发展的影响。通过将孟德尔随机化技术应用于这些代谢标志物,有可能揭示与LDH的潜在因果关系,为其预防和治疗干预提供新的视角。本研究采用两样本孟德尔随机化(MR)方法,利用来自2个独立来源的数据集,探讨血液和尿液中发现的35种代谢物与LDH发生之间的关联。通过逆方差加权法等方法进行MR分析得到的最显著结果,通过荟萃分析进一步评估。为提高结果的可靠性,应用多种校正方法调整显著性阈值。最后,进行反向MR分析,以确认所选代谢物对LDH的方向性因果影响。利用芬兰基因库R10和英国生物银行数据库的数据,进行MR分析以研究35种血液和尿液代谢物与LDH之间的关系。两组MR分析中使用逆方差加权法得出的最显著结果,随后进行荟萃分析。在荟萃分析中对显著性阈值应用了多种校正,得出优势比为0.860(95%置信区间:0.795 - 0.930,P = 0.0052)。此外,在任一数据集中,所鉴定的正向代谢物与LDH均未表现出反向因果关系。载脂蛋白是预防LDH的保护因素,可能降低发病风险并减缓其进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb5/12187337/bc693befb16d/medi-104-e42749-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb5/12187337/1b1376322dc1/medi-104-e42749-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb5/12187337/bc693befb16d/medi-104-e42749-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb5/12187337/1b1376322dc1/medi-104-e42749-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb5/12187337/ef5432caa07a/medi-104-e42749-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb5/12187337/165bfff2cf39/medi-104-e42749-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb5/12187337/bc693befb16d/medi-104-e42749-g004.jpg

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Lumbar disc herniation is an independent predictor of plaque burden in the patients with unstable angina.
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