Wang Hao, Cheng Ziji, Xu Zixuan, Wang Min, Sun Xingyang, Liu Wen, Wang Jingtian, Yang Qian, Zhang Tuo, Song Jie, Du Yanjun, Zhang Xiaoming
College of Acupuncture-Moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan, China.
Department of Anatomy, College of Chinese Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Brain Behav. 2025 Apr;15(4):e70478. doi: 10.1002/brb3.70478.
The present study employed Mendelian randomization to scrutinize the causal connections that may exist between 91 distinct inflammatory markers and six neuropsychiatric disorders, namely Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), anxiety disorders (ANX), depressive disorders (DEP), and unexplained encephalopathy (UE).
The methodology utilized involved the standard inverse variance weighting method within a two-sample, two-way Mendelian randomization framework and integrated statistics from genome-wide association studies. To ascertain the robustness of the identified causal associations, sensitivity analyses were performed with the aid of the MR-Egger method and the weighted median test.
The results revealed that 14 distinct systemic inflammatory modulators are potentially causally linked to the risk of developing various neuropsychiatric disorders. Specifically, five were associated with AD, eight with ANX, six with DEP, and one with UE. However, the causal associations involving systemic inflammatory markers with PD and MS require further investigation, particularly with the identification of additional significant genetic variants. Furthermore, the concentration levels of 33 systemic inflammatory factors could be modulated by the occurrence of neuropsychiatric conditions, indicated by this study. These include five affected by AD, eight by PD, six by MS, 12 by ANX, five by DEP, and five by UE.
本研究采用孟德尔随机化方法，以探究91种不同炎症标志物与六种神经精神疾病之间可能存在的因果关系，这六种疾病分别是阿尔茨海默病（AD）、多发性硬化症（MS）、帕金森病（PD）、焦虑症（ANX）、抑郁症（DEP）和不明原因脑病（UE）。
所采用的方法涉及在双样本、双向孟德尔随机化框架内的标准逆方差加权法，并整合了全基因组关联研究的统计数据。为确定所识别因果关联的稳健性，借助MR-Egger方法和加权中位数检验进行了敏感性分析。
结果显示，14种不同的全身炎症调节因子可能与多种神经精神疾病的发病风险存在因果关联。具体而言，有5种与AD相关，8种与ANX相关，6种与DEP相关，1种与UE相关。然而，涉及全身炎症标志物与PD和MS的因果关联需要进一步研究，特别是要识别更多显著的基因变异。此外，本研究表明，33种全身炎症因子的浓度水平可能会受到神经精神疾病发生的调节。其中包括5种受AD影响，8种受PD影响，6种受MS影响，12种受ANX影响，5种受DEP影响，5种受UE影响。
