GENOMIC ARCHITECTURE AND MOLECULAR DETERMINANTS IN MIGRAINE PATHOPHYSIOLOGY: AN INTEGRATIVE REVIEW

Abstract

This article aimed to synthesize evidence regarding the genomic architecture and molecular determinants of migraine. The methodology integrated GWAS, TWAS, and proteomics studies. The results reveal a complex architecture characterized by a dichotomy between rare monogenic forms—such as familial hemiplegic migraine (involving the *CACNA1A*, *ATP1A2*, *SCN1A*, and *PRRT2* genes)—and common polygenic forms. Recent advances have identified 123 risk loci, reinforcing the condition's neurovascular nature through gene enrichment in brain and vascular tissues. Determinants such as *CALCA*/*CALCB* (CGRP) and *HTR1F* validate modern therapeutic targets, while the *REV1* and *SREBF2* genes implicate DNA repair and cholesterol metabolism in the disease. Pleiotropy with psychiatric comorbidities underscores the biological complexity and global socioeconomic impact involved. These findings indicate that understanding molecular networks is vital for implementing precision medicine. This enables personalized, targeted interventions based on individual genetic risk profiles, aiming to optimize therapeutic responses and reduce disability.