Scholarlink

Background <p>Migraine is a highly prevalent neurological disorder with complex pathophysiology and limited treatment efficacy. Emerging evidence suggests immune cell involvement in migraine, but the specific regulatory mechanisms remain unclear. This study aimed to identify immune cell-type-specific genetic drivers of migraine and prioritize potential therapeutic targets.</p> Methods <p>We conducted a Mendelian randomization (MR) analysis integrating single-cell expression quantitative trait loci (sc-eQTL) data from 14 immune cell types with large-scale genome-wide association studies (GWAS) of migraine. Colocalization analysis, protein-protein interaction (PPI) networks, linkage disequilibrium score regression (LDSC), phenome-wide association studies (PheWAS), and drug repurposing databases were utilized to validate findings and assess therapeutic potential and safety.</p> Results <p>We identified 25 immune cell-specific eGenes causally associated with migraine, including <i>CDC42</i>, <i>NELFCD</i>, <i>HOXB3</i>, <i>HAX1</i>, and <i>FHL3</i>. Several genes, such as <i>CDC42</i> and <i>HAX1</i>, were implicated across multiple immune cell types. Subtype-specific analyses revealed differential gene effects in migraine with aura (MA) and without aura (MO). Genetic correlation and pleiotropy analyses linked eGenes to comorbid traits such as depression, gastrointestinal disorders, and blood pressure. PheWAS suggested minimal adverse associations for prioritized genes like <i>GINM1</i> and <i>TMA7</i>. Drug repurposing identified FDA-approved agents, including hydroxychloroquine sulfate (<i>NELFCD</i>) and bazedoxifene (<i>CDC42</i>), as potential migraine therapies.</p> Conclusion <p>This study reveals immune cell-specific genetic contributors to migraine and highlights druggable targets for therapeutic development. Integrating sc-eQTL with multi-omics and pharmacological data provides a novel framework for precision medicine in migraine.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dissecting immune cell-specific genetics in migraine: a multi-omics framework for target discovery and therapeutic prioritization

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月30日

查看全文
  • Yanggang Hong,
  • Yuze Mi,
  • Feng Chen,
  • Yirong Wang,
  • Jiajun Li,
  • Zhendi Shu

摘要

Background

Migraine is a highly prevalent neurological disorder with complex pathophysiology and limited treatment efficacy. Emerging evidence suggests immune cell involvement in migraine, but the specific regulatory mechanisms remain unclear. This study aimed to identify immune cell-type-specific genetic drivers of migraine and prioritize potential therapeutic targets.

Methods

We conducted a Mendelian randomization (MR) analysis integrating single-cell expression quantitative trait loci (sc-eQTL) data from 14 immune cell types with large-scale genome-wide association studies (GWAS) of migraine. Colocalization analysis, protein-protein interaction (PPI) networks, linkage disequilibrium score regression (LDSC), phenome-wide association studies (PheWAS), and drug repurposing databases were utilized to validate findings and assess therapeutic potential and safety.

Results

We identified 25 immune cell-specific eGenes causally associated with migraine, including CDC42, NELFCD, HOXB3, HAX1, and FHL3. Several genes, such as CDC42 and HAX1, were implicated across multiple immune cell types. Subtype-specific analyses revealed differential gene effects in migraine with aura (MA) and without aura (MO). Genetic correlation and pleiotropy analyses linked eGenes to comorbid traits such as depression, gastrointestinal disorders, and blood pressure. PheWAS suggested minimal adverse associations for prioritized genes like GINM1 and TMA7. Drug repurposing identified FDA-approved agents, including hydroxychloroquine sulfate (NELFCD) and bazedoxifene (CDC42), as potential migraine therapies.

Conclusion

This study reveals immune cell-specific genetic contributors to migraine and highlights druggable targets for therapeutic development. Integrating sc-eQTL with multi-omics and pharmacological data provides a novel framework for precision medicine in migraine.