Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Neuroinflammation. 2022 Apr 5;19(1):79. doi: 10.1186/s12974-022-02443-9.
Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) has been described as a biomarker for microglial activation, which were observed increased in a variety of neurological disorders.
Our objective was to explore whether genetically determined CSF sTREM2 levels are causally associated with different neurological diseases by conducting a two-sample Mendelian randomization (MR) study.
Single nucleotide polymorphisms significantly associated with CSF sTREM2 levels were selected as instrumental variables to estimate the causal effects on clinically common neurological diseases, including stroke, Alzheimer's diseases, Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis, and epilepsy and their subtypes. Summary-level statistics of both exposure and outcomes were applied in an MR framework.
Genetically predicted per 1 pg/dL increase of CSF sTREM2 levels was associated with higher risk of multiple sclerosis (OR = 1.038, 95%CI = 1.014-1.064, p = 0.002). Null association was found in risk of other included neurological disorders.
These findings provide support for a potential causal relationship between elevated CSF sTREM2 levels and higher risk of multiple sclerosis.
脑脊液（CSF）中可溶性髓系细胞触发受体 2（sTREM2）被描述为小胶质细胞激活的生物标志物，在各种神经疾病中观察到其水平升高。
通过进行两样本孟德尔随机化（MR）研究，我们旨在探索遗传决定的 CSF sTREM2 水平是否与不同的神经疾病存在因果关系。
选择与 CSF sTREM2 水平显著相关的单核苷酸多态性作为工具变量，以估计其对临床上常见的神经疾病（包括中风、阿尔茨海默病、帕金森病、肌萎缩侧索硬化症、多发性硬化症、癫痫及其亚型）的因果效应。采用 MR 框架应用暴露和结局的汇总统计数据。
CSF sTREM2 水平每增加 1 pg/dL，与多发性硬化症的风险增加相关（OR=1.038，95%CI=1.014-1.064，p=0.002）。在其他纳入的神经疾病的风险中未发现关联。
这些发现为 CSF sTREM2 水平升高与多发性硬化症风险增加之间存在潜在因果关系提供了支持。
