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.
Cluster headaches affect 0.1% of the population and are four times more common in males than in females. Patients with this condition present with severe unilateral head pain localized in the frontotemporal lobe, accompanied by ipsilateral lacrimation, conjunctival injection, nasal congestion, diaphoresis, miosis, and eyelid edema. Recently, the first genome-wide association study of cluster headaches was conducted with the goal of aggregating data for meta-analyses, identifying genetic risk variants, and gaining biological insights. Although little is known about the pathophysiology of cluster headaches, the trigeminovascular and trigeminal autonomic reflexes and hypothalamic pathways are involved. Among anti-calcitonin gene-related peptide monoclonal antibodies, galcanezumab has been reported to be effective in preventing episodic cluster headaches.
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