Genetics of migraine: an update

Abstract

An important genetic component of migraine was systematically established by epidemiological studies in the 1990s. Over the past 15 years, significant progress has been made in unraveling the genetic basis and pathophysiological mechanisms of familial hemiplegic migraine, a rare and severe autosomal-dominant subtype of migraine with aura. Three different causative genes (CACNA1A, ATP1A2 and SCN1A), all of which are involved in cerebral ion translocation, have been identified. Functional studies and mouse models have shown that mutations in these genes, by different mechanisms, cause a disturbed cerebral glutamate homeostasis and, thus, increase susceptibility to cortical spreading depression, the likely correlate of migraine aura. More recently, genome-wide association studies have, for the first time, detected robust risk variants associated with the more common, genetically complex types of migraine, which has generated new perspectives for genetic research in migraine. This review summarizes the current knowledge about migraine genetics, with a focus on both familial hemiplegic migraine and recent results of genome-wide association studies.