Inflammo-immune perspective on the association of eight migraine risk factors with migraine: a multi-omics Mendelian randomization study

Background: Migraine risk factors are associated with migraine susceptibility, yet their mechanisms are unclear. Evidence suggests a role for inflammatory proteins and immune cells in migraine pathogenesis. This study aimed to examine the inflammo-immune association between eight migraine risk factors and the disorder. Methods: This study utilized inverse variance weighted (IVW) method and colocalization analysis to explore potential causal relationships between eight migraine risk factors, migraine, 731 immune cells, and 91 circulating inflammatory proteins. Mediation Mendelian randomization (MR) was further used to confirm the mediating role of circulating inflammatory proteins and immune cells between the eight migraine risk factors and migraine. Results: Migraine risk factors are linked to 276 immune cells and inflammatory proteins, with cigarettes smoked per day strongly co-localized with CD33-HLA DR+ cells. Despite no co-localization, 23 immune cells/inflammatory proteins relate to migraine. Depression, all anxiety disorders, and sleep apnea are correlated with migraine, and all anxiety disorders are supported by strong co-localization evidence. However, the mediating effect of inflammatory proteins and immune cells between eight migraine risk factors and migraine has not been confirmed. Conclusion: We elucidate the potential causal relationships between eight migraine risk factors, migraine, immune cells, and inflammatory proteins, enhancing our understanding of the molecular etiology of migraine pathogenesis from an inflammatory-immune perspective.