Causal Associations of Immune Cell Phenotypes with Migraine: A Mendelian Randomization Study

Background The interaction between the immune system and the brain, crucial for blood-brain barrier integrity, is a potential factor in migraine development. Although there's evidence of a connection between immune dysregulation and migraine, a clear causal link has been lacking. To bridge this knowledge gap, we performed an MR analysis of 731 immune cell phenotypes to determine their causality with migraine. Aim Our goal was to use MR analysis on 731 immune cell markers to investigate their causal links to migraine, aiming to deepen our understanding of the immune-brain axis in migraine and uncover new therapeutic targets. Methods We applied a two-sample MR method to assess causality between immune cell markers and migraine, analyzing 731 phenotypes from genetic data. Parameters included fluorescence, cell abundance, count, and morphology. Sensitivity and pleiotropy checks validated our findings. Results After applying a false discovery rate correction, our Mendelian randomization study identified 35 of 731 immune phenotypes with a significant causal link to migraine (P < 0.05). Of these, 24 showed a protective effect (inverse variance weighting < 0.05, odds ratio < 1), and 11 were risk factors (inverse variance weighting ≥ 0.05, odds ratio ≥ 1). Conclusion Our study uncovers a significant genetic link between certain immune cell markers and migraine, providing new insights into the disorder's pathophysiology. These discoveries are crucial for developing targeted biomarkers and personalized treatments. The research enhances our understanding of immune cells' role in migraine and may substantially improve patient outcomes and lessen its socio-economic impact.