The molecular genetics of migraine: toward the identification of responsible genes

Migraine is a complex debilitating neurovascular disease affecting approximately 15% of the Western populations. Familial clustering, twin studies and segregation analyses suggest that migraine has a significant genetic component, but the number of genes involved remains unclear. The progress in migraine genetics has recently jumped ahead with the identification of genes responsible for Familiar Hemiplegic Migraine (FHM), a rare subtype of migraine with aura showing autosomal dominant mode of inheritance. Nevertheless, the knowledge about common types of migraine has been particularly rewarding and recently, seven loci with significant linkage to migraine with or without aura have been identified on 1q31, 4q24, 6p12.2-21.1, 11q24, 14q21.2-q22.3, 15q11-q13 and Xq24-28, suggesting the presence of migraine susceptibility genes in these regions. Identification of genes predisposing to the more common and genetically complex forms of migraine has been complicated by clinical and genetic heterogeneity of the disease. The major challenge in the coming years facing biomedical research of migraine is the identification of disease-susceptibility genes and the understanding of how migraine risk can be influenced by the interaction of these variants with each other and with specific environmental factors in order to provide individuals with clinically-useful diagnostic, prognostic and therapeutic information. This paper briefly summarizes the previous knowledge and highlights some recent developments in the complex genetic nature of migraine