The 1400 metabolite-mediated relationship between 91 inflammatory cytokines and migraine: An exploratory two-step Mendelian randomization study

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL European Journal of Clinical Investigation Pub Date : 2024-09-15 DOI:10.1111/eci.14316

Huiqi Sun, Xutong Lv, Dongbin Zhang, Yue Shen, Hongxiu Lu

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Abstract

Background

Inflammatory cytokines and migraines have been associated in previous research, but the underlying mechanisms of action are still elusive. The biological functions of metabolites are crucial in the onset of migraine. Our goals were to clarify the cause-and-effect connection between inflammatory cytokines and migraines and explore the potential mediating function of metabolites.

Methods

Utilizing summary-level data from genome-wide association studies (GWAS), we conducted two-sample Mendelian randomization (MR) analyses to evaluate the possible causal connection between inflammatory cytokines and migraines. A two-step MR analysis was employed to further investigate the potential mediating pathways of metabolites.

Results

MR analysis identified a total of 9 inflammatory cytokines that were genetically associated with migraines, and we subsequently identified 21 mediated relationships, with 20 metabolites (13 metabolites, 7 ratios) acting as potential mediators between 8 inflammatory cytokines and migraine. The 9 inflammatory cytokines were beta-nerve growth factor levels (β-NGF), T-cell surface glycoprotein CD5 levels (CD5), T-cell surface glycoprotein CD6 isoform levels (CD6), C-X-C motif chemokine 11 levels (CXCL11), interleukin-4 levels (IL-4), oncostatin-M levels (OSM), signalling lymphocytic activation molecule levels (SLAM), C-C motif chemokine 25 levels (CCL25) and monocyte chemoattractant protein-1 levels (MCP-1).

Conclusion

Our research findings provide evidence for both a causal connection between inflammatory cytokines and migraines, as well as a metabolite-mediated pathway. These biomarkers facilitate the detection, diagnosis and treatment of migraines while offering fresh perspectives on their underlying mechanisms.

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1400 个代谢物介导的 91 种炎症细胞因子与偏头痛之间的关系：一项探索性两步孟德尔随机研究。

背景：在以往的研究中，炎性细胞因子与偏头痛有关联，但其潜在的作用机制仍然难以捉摸。代谢物的生物功能对偏头痛的发病至关重要。我们的目标是阐明炎性细胞因子与偏头痛之间的因果关系，并探索代谢物的潜在中介功能：利用全基因组关联研究（GWAS）的汇总数据，我们进行了双样本孟德尔随机化（MR）分析，以评估炎性细胞因子与偏头痛之间可能存在的因果关系。为了进一步研究代谢物的潜在中介途径，我们采用了两步 MR 分析法：结果：磁共振分析共发现9种炎症细胞因子与偏头痛存在遗传相关性，随后我们又发现了21种介导关系，其中20种代谢物（13种代谢物，7种比率）是8种炎症细胞因子与偏头痛之间的潜在介导物。这 9 种炎症细胞因子分别是：β-神经生长因子水平（β-NGF）、T 细胞表面糖蛋白 CD5 水平（CD5）、T 细胞表面糖蛋白 CD6 异构体水平（CD6）、C-X-C 矩阵趋化因子 11 水平（CXCL11）、白细胞介素-4水平（IL-4）、oncostatin-M水平（OSM）、信号淋巴细胞活化分子水平（SLAM）、C-C动因趋化因子25水平（CCL25）和单核细胞趋化蛋白-1水平（MCP-1）。结论我们的研究结果为炎性细胞因子与偏头痛之间的因果关系以及代谢物介导的途径提供了证据。这些生物标志物有助于偏头痛的检测、诊断和治疗，同时为偏头痛的内在机制提供了新的视角。

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来源期刊

European Journal of Clinical Investigation 医学-医学：内科

CiteScore

9.50

自引率

3.60%

发文量

192

审稿时长

1 months

期刊介绍： EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.