Authors
Xin Mo, Dongren Sun, Fangfang Li, Danqi Wang, Yunjiao Deng, Yiwei Liao, Xiaosu Yang, Haiting Zhao
Published in
The journal of headache and pain. Volume 27. Issue 1. Jul 25, 2026. Epub Jul 25, 2026.
Abstract
Migraine frequently co-occurs with psychiatric disorders, yet the immunogenetic mechanisms linking these conditions remain largely unexplored.
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.
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.
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.
Not applicable.
PMID:
42581340
Bibliographic data and abstract were imported from PubMed on 12 Aug 2026.
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