Migraine genetics

Abstract

Migraine with aura (MA) and migraine without aura (MO) are primary headaches prevalent in the general population that carry a substantial familial liability. Based on the model of migraine as a complex disease, a multifactorial type of inheritance has been suggested, but familial hemiplegic migraine (FHM), classified as a subtype of MA, shows an autosomal dominant transmission pattern and is due to mutations in three genes encoding for neural channel subunits. These FHM mutations, however, account for a minority of the FHM families and are not usually found in sporadic HM or in the typical migraines MA/MO. This implies that the genetic predisposition to the typical migraines may be different and that FHM could be better classified as a type of syndromic migraine rather than a MA subtype. Linkage and genome-wide scans have disclosed several chromosomal liability loci in selected families with MA/MO. It is likely that typical migraine genes will be discovered in the future. Epigenetic mechanisms, especially those acting in the early stages of neural development, are here proposed to be involved in the genetics of the typical migraines, especially if the typical migraines are modeled as evolutionarily conserved behaviors (sickness behavior) enacted out of a genetic repertoire.