Tong Dan, Zhang Xinyue, Xiao Zhiyong, Taothong Supattra, Teeravarunyou Prapawee, Wu Wanxia, Wu Sai, Chen Nuo, Tao Siyuan, Zhou Jun, Song Qian, Liang Fanrong, Li Zhengjie
Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People's Republic of China.
Key Laboratory of Acupuncture for Senile Disease (Chengdu University of TCM), Ministry of Education, Chengdu, Sichuan, People's Republic of China.
J Pain Res. 2025 Jul 9;18:3429-3438. doi: 10.2147/JPR.S521100. eCollection 2025.
This study aims to investigate the potential causal relationship between migraine and white matter (WM) structural connectivity using genetic data and the Mendelian randomization (MR) analyses method.
Genome-wide association study (GWAS) summary statistics for migraine (48,975 cases/540,381 controls) and 206 WM structural connectivity related imaging-derived phenotypes (IDPs) (26,333 samples) were collected. Based on instrumental variables (IVs) selected from the GWAS summary statistics, the bidirectional two-sample MR analyses were conducted to infer bidirectional causal associations between migraine and WM structural connectivity. The inverse variance-weighted (IVW) method served as the primary approach for analyzing causality.
In the forward MR analysis, it was found that migraine had a significant effect on right hemisphere somatomotor network to amygdala WM structural connectivity (IVW-derived = 0.11, 95% CI = [0.04, 0.17], = 1.02e-03, FDR = 0.04). While in the reverse MR analysis, no causal link was detected between WM structural connectivity and migraine.
This study provides genetic evidences for a causal relationship between migraine and WM structural connectivity. These findings provide new perspectives for the understanding of neuropathology and symptomatology in migraine and might provide a potential therapeutic target for future migraine treatment research.
本研究旨在利用遗传数据和孟德尔随机化（MR）分析方法，探讨偏头痛与白质（WM）结构连通性之间的潜在因果关系。
收集了偏头痛（48,975例/540,381例对照）的全基因组关联研究（GWAS）汇总统计数据以及206种与WM结构连通性相关的影像衍生表型（IDP）（26,333个样本）。基于从GWAS汇总统计数据中选择的工具变量（IV），进行双向双样本MR分析，以推断偏头痛与WM结构连通性之间的双向因果关联。逆方差加权（IVW）方法作为分析因果关系的主要方法。
在前瞻性MR分析中，发现偏头痛对右半球躯体运动网络至杏仁核的WM结构连通性有显著影响（IVW衍生值 = 0.11，95%置信区间 = [0.04, 0.17]，P = 1.02e-03，FDR = 0.04）。而在反向MR分析中，未检测到WM结构连通性与偏头痛之间的因果联系。
本研究为偏头痛与WM结构连通性之间的因果关系提供了遗传学证据。这些发现为理解偏头痛的神经病理学和症状学提供了新的视角，并可能为未来偏头痛治疗研究提供潜在的治疗靶点。
