Table_2_Two-sample Mendelian randomization analysis of 91 circulating inflammatory protein levels and amyotrophic lateral sclerosis.XLS

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.

引言 肌萎缩侧索硬化症（Amyotrophic Lateral Sclerosis, ALS）是一种病理生理学机制尚未明确的神经退行性疾病。近期研究凸显了全身性炎症，尤其是循环炎症蛋白在ALS发病进程中的作用。
方法 本研究旨在探究此类循环炎症蛋白与ALS之间潜在的因果关联。我们采用双样本孟德尔随机化（two-sample Mendelian Randomization, MR）方法，基于大规模全基因组关联研究数据，分析了91种循环炎症蛋白与ALS的关联。研究涵盖了MR Egger法、加权中位数法、逆方差加权法等多种MR分析策略，并辅以敏感性分析以保障结果的稳健性。
结果 研究观察到，腺苷脱氨酶、白细胞介素-17C、制瘤素M、白血病抑制因子受体以及骨保护素等炎症蛋白的水平与ALS患病风险存在显著关联，且该关联在不同P值阈值下均保持一致。双向孟德尔随机化分析提示，ALS患病风险可能会影响部分炎症蛋白的水平。
讨论 本研究通过孟德尔随机化分析证实，循环炎症蛋白与ALS之间存在潜在的因果关联。该发现为ALS的病理生理学机制研究提供了全新视角，并提示了潜在的治疗靶点。未来仍需开展进一步研究以验证本研究结果，并明确此类蛋白在ALS发病中的具体作用。