Causal associations of immune cell phenotypes with migraine: A mendelian randomization study

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 a two-sample Mendelian randomization (MR) analysis of 731 immune cell phenotypes to determine their causality with migraine, of which parameters included fluorescence, cell abundance, count, and morphology. Sensitivity and pleiotropy checks validated our findings. After applying a false discovery rate correction, our MR 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 : p < 0.05, odds ratio <1), and 11 were risk factors (inverse variance weighting : p < 0.05, odds ratio >1). Although limited by population sample size and potential population-specific genetic variations, 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.