IntroductionAmyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood pathophysiology. Recent studies have highlighted systemic inflammation, especially the role of circulating inflammatory proteins, in ALS.MethodsThis study investigates the potential causal link between these proteins and ALS. We employed a two-sample Mendelian Randomization(MR) approach, analyzing data from large-scale genome-wide association studies to explore the relationship between 91 circulating inflammatory proteins and ALS. This included various MR methods like MR Egger, weighted median, and inverse-variance weighted, complemented by sensitivity analyses for robust results.ResultsSignificant associations were observed between levels of inflammatory proteins, including Adenosine Deaminase, Interleukin-17C, Oncostatin-M, Leukemia Inhibitory Factor Receptor, and Osteoprotegerin, and ALS risk. Consistencies were noted across different P-value thresholds. Bidirectional MR suggested that ALS risk might influence levels of certain inflammatory proteins.DiscussionOur findings, via MR analysis, indicate a potential causal relationship between circulating inflammatory proteins and ALS. This sheds new light on ALS pathophysiology and suggests possible therapeutic targets. Further research is required to confirm these results and understand the specific roles of these proteins in ALS.

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91 种循环炎症蛋白水平和肌萎缩侧索硬化症的两样本孟德尔随机化分析

简介肌萎缩侧索硬化症（ALS）是一种神经退行性疾病，其病理生理学知之甚少。最近的研究强调了全身炎症，特别是循环炎症蛋白在 ALS 中的作用。方法本研究调查了这些蛋白与 ALS 之间的潜在因果关系。我们采用双样本孟德尔随机化 (MR) 方法，分析大规模全基因组关联研究的数据，以探索 91 种循环炎症蛋白与 ALS 之间的关系。这包括各种 MR 方法，如 MR Egger、加权中位数和逆方差加权，并辅以敏感性分析以获得稳健的结果。 结果观察到炎症蛋白水平之间存在显着关联，包括腺苷脱氨酶、白介素-17C、制瘤素-M、白血病抑制蛋白因子受体、骨保护素和 ALS 风险。不同领域之间存在一致性磷- 值阈值。双向 MR 表明 ALS 风险可能会影响某些炎症蛋白的水平。讨论通过 MR 分析，我们的发现表明循环炎症蛋白与 ALS 之间存在潜在因果关系。这为 ALS 病理生理学提供了新的线索，并提出了可能的治疗目标。需要进一步的研究来证实这些结果并了解这些蛋白质在 ALS 中的具体作用。