A mendelian randomization analysis of the associations between haptoglobin and multiple sclerosis.

IF 2.7 4区医学 Q2 CLINICAL NEUROLOGY Neurological Sciences Pub Date : 2024-12-01 Epub Date: 2024-10-14 DOI:10.1007/s10072-024-07786-0

Xingxiao Huang, Qian Zeng, Yachun Hu, Xiaolei Shi

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Abstract

Background: Observational studies have suggested an association between plasma haptoglobin and multiple sclerosis (MS). Haptoglobin plays an important role in the pathogenesis of MS. However, whether it has a causal effect on MS remains unknown.

Methods: We here used a two-sample bidirectional Mendelian randomization (MR) method to investigate the causality between haptoglobin and MS. Genetic variants associated with plasma haptoglobin from two independent genome wide association studies (GWASs) (used as the discovery and replication datasets, respectively) were applied as the exposure. Their causal effects on summary statistics of GWASs of MS and disease severity were evaluated using the inverse-variance weighted (IVW) approach as the main analysis component.

Results: We found in both discovery and replication dataset that plasma haptoglobin was causally positively associated with the risk of MS (discovery: OR: 1.063, 95% CI: 1.022-1.106, P = 0.002; replication: OR: 1.041, 95% CI: 1.005-1.078, P = 0.026), but it was not associated with MS severity (discovery: OR: 1.017, 95% CI: 0.993-1.042, P = 0.168; replication: OR: 1.011, 95% CI: 0.987-1.036, P = 0.373). Besides, we did not detect any significant results in the reverse causation analysis.

Conclusions: Our study provides evidence for the causal effects of plasma haptoglobin on the risk of MS.

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对血红蛋白与多发性硬化症之间关系的 "孟德尔随机分析"。

背景：观察性研究表明，血浆隐血素与多发性硬化症（MS）之间存在关联。血红蛋白在多发性硬化症的发病机制中起着重要作用。然而，它是否对多发性硬化症有因果关系仍是未知数：方法：我们采用双样本双向孟德尔随机化（MR）方法研究了嗜血红蛋白与多发性硬化症之间的因果关系。两个独立的全基因组关联研究（GWAS）（分别作为发现数据集和复制数据集）中与血浆血红蛋白相关的遗传变异被用作暴露。使用反方差加权（IVW）方法作为主要分析组件，评估了它们对多发性硬化症和疾病严重程度的 GWASs 概要统计的因果效应：结果：我们在发现和复制数据集中都发现，血浆高铁血红蛋白与多发性硬化症的发病风险呈因果正相关（发现：OR：1.063，95%；复制：OR：1.063，95%；发现：OR：1.063，95%）：OR: 1.063, 95% CI: 1.022-1.106, P = 0.002; replication：OR：1.041，95% CI：1.005-1.078，P = 0.026），但与多发性硬化症的严重程度无关（发现：OR：1.017，95% CI：1.005-1.078，P = 0.026）：OR: 1.017, 95% CI: 0.993-1.042, P = 0.168; replication：OR：1.011，95% CI：0.987-1.036，P = 0.373）。此外，我们在反向因果关系分析中未发现任何显著结果：我们的研究为血浆高铁血红蛋白对多发性硬化症风险的因果效应提供了证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurological Sciences 医学-临床神经学

CiteScore

6.10

自引率

3.00%

发文量

743

审稿时长

4 months

期刊介绍： Neurological Sciences is intended to provide a medium for the communication of results and ideas in the field of neuroscience. The journal welcomes contributions in both the basic and clinical aspects of the neurosciences. The official language of the journal is English. Reports are published in the form of original articles, short communications, editorials, reviews and letters to the editor. Original articles present the results of experimental or clinical studies in the neurosciences, while short communications are succinct reports permitting the rapid publication of novel results. Original contributions may be submitted for the special sections History of Neurology, Health Care and Neurological Digressions - a forum for cultural topics related to the neurosciences. The journal also publishes correspondence book reviews, meeting reports and announcements.