A Bidirectional Mendelian Randomization Study of Causal Relationships Between Migraine and White-Matter Structural Connectivity.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.