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 β = 0.11, 95% CI = [0.04, 0.17], p = 1.02e-03, FDR p = 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.