Genetic Architecture of Migraine: From Broad Insights to East Asian Perspectives

Migraine is a complex neurological disorder with a strong genetic component, ranging from rare monogenic forms, such as familial hemiplegic migraine (FHM), to common polygenic migraine. FHM is primarily caused by mutations in CACNA1A, ATP1A2, and SCN1A, which affect ion channel function and cortical excitability. Additional genes, including PRRT2, have also been implicated, broadening the genetic landscape of monogenic migraine. Genome-wide association studies (GWAS) have identified multiple susceptibility loci for common migraine, highlighting key pathways related to neuronal excitability and vascular function. These findings have reinforced the neurovascular hypothesis of migraine pathogenesis. GWAS on other headache disorders, such as broadly defined headache or cluster headache, have also revealed both overlapping and distinct genetic risk factors. Genetic studies in East Asians have identified both ancestry-specific risk variants and overlapping loci with European populations, suggesting similarities in biological pathways while also highlighting population-specific differences in migraine susceptibility. Expanding research on the genetics of migraine in East Asian populations is essential for uncovering novel risk factors and improving the generalizability of genetic findings.