单核细胞趋化蛋白-1水平与神经精神疾病之间的因果关系：来自大规模遗传数据的证据。

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology Pub Date : 2025-10-04 DOI:10.1016/j.jneuroim.2025.578767

Yuyao He , Wenyue Hu , Yanliang Li , Zhenyun Han

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引用次数: 0

摘要

目的：采用双样本孟德尔随机化（MR）方法，探讨单核细胞趋化蛋白-1 （MCP-1）水平与阿尔茨海默病（AD）、血管性痴呆（VD）、抑郁症、精神分裂症（SCZ）和焦虑症等神经精神疾病（npd）风险的因果关系。方法：利用全基因组关联研究（GWAS）的汇总统计数据来检验MCP-1水平与npd之间的关系。MCP-1汇总数据来自IEU OpenGWAS数据库，而npd的GWAS汇总统计数据主要来自FinnGen联盟，其他复制数据集来自IEU OpenGWAS和UK Biobank。主要的分析方法是反方差加权（IVW）方法，补充加权中位数，MR- egger回归，以及双向MR分析的加权和简单模式方法。采用Cochran’s Q检验评估异质性，采用MR-Egger回归和MR-PRESSO检验评估水平多效性。使用荟萃分析对多个GWAS来源的结果进行综合，以提供可靠和全面的估计。结果：在初级MR分析中，IVW结果显示MCP-1水平升高与AD （OR: 1.108; 95% CI: 1.003-1.224; PIVW = 0.044）和SCZ （OR: 1.245, 95% CI: 1.014-1.529, PIVW = 0.036）风险增加有统计学意义。未观察到水平多效性的证据（P < 0.05），留一敏感性分析支持这些发现的稳健性。然而，在复制MR分析中，没有发现MCP-1与任何npd的因果关系（PIVW 0.05）。meta分析进一步证实了MCP-1水平与AD风险之间的显著相关性（OR: 1.096, 95% CI: 1.017-1.182, P = 0.017），而其他npd之间没有显著的因果关系。结论：MCP-1水平升高与阿尔茨海默病风险有因果关系，但与其他npd无关，这表明MCP-1在AD中具有疾病特异性作用和治疗潜力。

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Causal relationships between monocyte chemoattractant protein-1 levels and neuropsychiatric disorders: Evidence from large-scale genetic data

Objective

To investigate the causal relationship between monocyte chemoattractant protein-1 (MCP-1) levels and risk of neuropsychiatric disorders (NPDs), including Alzheimer's disease (AD), vascular dementia (VD), depression, schizophrenia (SCZ), and anxiety disorders, using two-sample Mendelian randomization (MR).

Methods

Summary statistics from genome-wide association studies (GWAS) were utilized to examine the relationship between MCP-1 levels and NPDs. MCP-1 summary data were obtained from the IEU OpenGWAS database, while GWAS summary statistics for NPDs were primarily sourced from the FinnGen consortium, with additional replication datasets from the IEU OpenGWAS and UK Biobank. The primary analytical approach was the inverse-variance weighted (IVW) method, complemented by weighted median, MR-Egger regression, and both weighted and simple mode methods in bidirectional MR analyses. Heterogeneity was assessed using Cochran's Q test, and horizontal pleiotropy was evaluated using MR-Egger regression and the MR-PRESSO test. Results from multiple GWAS sources were synthesized using meta-analysis to provide robust and comprehensive estimates.

Results

In primary MR analysis, IVW results indicated a statistically significant association between elevated MCP-1 levels and increased risk of AD (OR: 1.108; 95 % CI: 1.003–1.224; P_IVW = 0.044) and SCZ (OR: 1.245, 95 % CI: 1.014–1.529, P_IVW = 0.036). No evidence of horizontal pleiotropy was observed (P > 0.05), and leave-one-out sensitivity analysis supported the robustness of these findings. However, no causal associations were identified in replication MR analyses for MCP-1 with any of the NPDs (P_IVW > 0.05). Meta-analysis further confirmed the significant association between MCP-1 levels and AD risk (OR: 1.096, 95 % CI: 1.017–1.182, P = 0.017), while no significant causal relationships were observed for the other NPDs.

Conclusion

Elevated MCP-1 levels are causally associated with Alzheimer's disease risk but not with other NPDs, indicating a disease-specific role and therapeutic potential in AD.

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来源期刊

Journal of neuroimmunology 医学-免疫学

CiteScore

6.10

自引率

3.00%

发文量

154

审稿时长

37 days

期刊介绍： The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication.