The genetics of migraine.

The search for genes involved in the pathophysiology of migraine poses major difficulties. First, there is no objective diagnostic method to assess the status of the individuals studied. Second, migraine is a polygenic multifactorial disorder. Familial hemiplegic migraine (FHM) is the only known autosomal dominant subtype of migraine. In half the families with FHM who have been studied, there are mutations in the calcium-channel gene CACNA1A, located on chromosome 19. In other families, a locus has been mapped on chromosome 1. The role of these loci in typical migraine is still unknown. A susceptibility locus for migraine with aura has been located on chromosome 19 (but is distinct from CACNA1A) and a genome-wide linkage analysis has mapped a susceptibility locus on chromosome 4. Another locus for migraine may be on the X chromosome. Finally, many positive association studies have been published, but few have been replicated.