Integrated Identification of NAD⁺ Metabolism-Associated Candidate Genes

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Migraine is a leading cause of disability worldwide.
• Many patients show poor response to existing migraine treatments.
• Neuro-immune interactions are increasingly recognized in migraine pathophysiology.

Purpose of the Study:

• To identify peripheral immune-related genes associated with NAD+ metabolism in migraine.
• To explore the link between systemic immunity, NAD+ metabolism, and migraine.

Main Methods:

• Integrated bulk and single-cell transcriptomic analyses of migraine patient data (PRJEB40032).
• Bioinformatic approaches including differential expression analysis, WGCNA, PPI networks, LASSO, SVM-RFE, and XGBoost for gene prioritization.
• Functional enrichment, immune cell composition analysis, and validation in a mouse model.

Main Results:

• CXCL8, CXCR4, CXCL1, and TNFAIP3 were identified as key candidate genes.
• These genes are linked to immune and inflammatory pathways (e.g., IL-17, NF-κB, TNF).
• Increased immune cell activity (NK, mast, eosinophils, neutrophils) and specific gene expression patterns were observed in migraine patients and a mouse model.

Conclusions:

• Peripheral immune genes associated with NAD+ metabolism are implicated in migraine.
• The findings suggest a potential connection between systemic immune dysregulation, NAD+ metabolism, and migraine.
• Prioritized genes offer novel avenues for migraine research and therapeutic development.