Migraine immune cell gene targets and their relationship to psychiatric disorders.

BACKGROUND: Migraine frequently co-occurs with psychiatric disorders, yet the immunogenetic mechanisms linking these conditions remain largely unexplored. METHODS: Using cis-eQTL data from 28 immune cell subtypes (1,925 donors) and GWAS summary statistics for migraine and five psychiatric disorders, we performed single-cell transcriptome-wide Mendelian randomization, Bayesian colocalization, genetic correlation, and cross-disease pleiotropy analyses. Independent replication was performed using external datasets. RESULTS: Migraine and its subtypes showed significant positive genetic correlations with all five psychiatric disorders (rg = 0.39-0.73). We identified 83 immune cell gene targets for migraine, 13 for migraine with aura, and 19 for migraine without aura. Among these, 6 targets showed shared associations with anxiety and 1 with depression. Three prioritized genes-HLA-A, CDK2AP1, and TTC24-demonstrated cross-disease pleiotropic effects. Notably, HLA-A in cDC1 exhibited discordant pleiotropy (protective for migraine with aura, risk for depression), with known drug-gene interactions involving antiepileptics and tricyclic antidepressants. CONCLUSIONS: These findings suggest that immune cell-specific genes, particularly HLA-A, CDK2AP1, and TTC24, may bridge migraine and psychiatric disorders, offering potential candidates for further investigation into shared immunogenetic mechanisms. CLINICAL TRIAL NUMBER: Not applicable.