Peng Yuhang, Zhang Xiaolin, Guo Jinhua, Chen Mingxin, Cheng Yuan, Yue Jianhe, Jiang Yongxiang
Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Osteology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Pain Res Manag. 2025 Jul 25;2025:8746245. doi: 10.1155/prm/8746245. eCollection 2025.
Trigeminal neuralgia (TN) is a prevalent neurological disorder characterized by recurrent acute pain localized within the distribution area of the trigeminal nerve. This condition places a severe psychological and emotional burden on patients. Although lipids are associated with many diseases, their relationship with TN remains unclear. This study aims to investigate the causal association between plasma lipidome and TN using a bidirectional two-sample Mendelian randomization (MR) approach, with the ultimate goal of informing potential therapeutic strategies for TN management. We conducted a bidirectional two-sample MR analysis to systematically assess the causal relationship between plasma lipidome and TN. Genome-wide association study (GWAS) summary statistics for plasma lipidome and TN were obtained from publicly available datasets. The primary causal inference was performed using inverse variance weighted (IVW) regression, with complementary analyses including MR-Egger regression, weighted mode, simple mode, weighted median, and MR pleiotropy residuals and outliers (MR-PRESSO) to test for and adjust potential pleiotropy. Comprehensive sensitivity analyses were implemented to verify the robustness of our findings, including heterogeneity testing, leave-one-out analysis, and examination of directional pleiotropy. This multianalytical approach provides a rigorous framework for elucidating the potential role of plasma lipidome dysregulation in TN pathogenesis. Our forward MR analysis results demonstrated that genetically predicted glycerophospholipids (GP) and glycerolipid family (GL) exert significant causal effects on TN risk. More specifically, phosphatidylinositol (PI) in the GP, as well as diacylglycerol and triacylglycerol in the GL, were significantly associated with reduced TN risk ( < 0.05, OR < 1). However, distinct molecular configurations of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) within the GP class exhibited differential impacts on TN susceptibility. The reverse MR analysis identified eight configurations of PC reduced TN risk ( < 0.05, OR < 1), with PC (18:0_18:2) showing a particularly notable bidirectional causal relationship with TN. Rigorous sensitivity analyses confirmed the absence of both heterogeneity (Cochran's > 0.05) and horizontal pleiotropy (MR-Egger intercept > 0.05) across all examined lipid species, supporting the robustness of these findings. This MR study establishes causal links between specific plasma lipidomes and TN risk, identifying protective lipid species and revealing a bidirectional relationship for PC, offering potential therapeutic targets for TN management.
三叉神经痛（TN）是一种常见的神经系统疾病，其特征为三叉神经分布区域内反复出现急性疼痛。这种疾病给患者带来了严重的心理和情感负担。尽管脂质与许多疾病有关，但其与TN的关系仍不清楚。本研究旨在使用双向双样本孟德尔随机化（MR）方法研究血浆脂质组与TN之间的因果关系，最终目标是为TN的潜在治疗策略提供依据。我们进行了双向双样本MR分析，以系统评估血浆脂质组与TN之间的因果关系。从公开可用的数据集中获取了血浆脂质组和TN的全基因组关联研究（GWAS）汇总统计数据。主要因果推断采用逆方差加权（IVW）回归进行，补充分析包括MR-Egger回归、加权模式、简单模式、加权中位数以及MR多效性残差和异常值（MR-PRESSO），以检验和调整潜在的多效性。实施了全面的敏感性分析以验证我们研究结果的稳健性，包括异质性检验、留一法分析以及方向性多效性检查。这种多分析方法为阐明血浆脂质组失调在TN发病机制中的潜在作用提供了一个严格的框架。我们的正向MR分析结果表明，基因预测的甘油磷脂（GP）和甘油脂家族（GL）对TN风险具有显著的因果效应。更具体地说，GP中的磷脂酰肌醇（PI）以及GL中的二酰甘油和三酰甘油与TN风险降低显著相关（<0.05，OR<1）。然而，GP类别中磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE）的不同分子构型对TN易感性表现出不同的影响。反向MR分析确定了8种PC构型可降低TN风险（<0.05，OR<1），其中PC（18:0_18:2）与TN呈现出特别显著的双向因果关系。严格的敏感性分析证实，在所有检测的脂质种类中均不存在异质性（ Cochr an's>0.05）和水平多效性（MR-Egger截距>0.05），支持了这些研究结果的稳健性。这项MR研究建立了特定血浆脂质组与TN风险之间的因果联系，确定了具有保护作用的脂质种类，并揭示了PC的双向关系，为TN的管理提供了潜在的治疗靶点。
