Genetics of migraine: an update.

Observations including the long-recognized tendency of migraine to run in families, the high concordance rates for migraine in twins reared together or apart, and the association of specific mutations with a rare migraine form are consistent with a genetic contribution to the disorder. This paper summarizes major findings to date on the genetics of migraine. Study of the heritability of migraine, particularly the common forms of migraine, is beset by several challenges including the absence of easily measurable biological markers, uncertainty about the etiologic and clinical overlap among migraine types, and the apparently complex interplay of environmental and genetic factors in determining migraine phenotype. Nevertheless, significant progress has been realized in recent years. Familial hemiplegic migraine, a rare migraine variant, appears to be transmitted by a Mendelian, autosomal dominant mode of inheritance involving mutations in at least 2 genes. These genes do not seem to be critically involved in the other forms of migraine; however, several other susceptibility loci for more common forms of migraine have been identified in recent genome-wide screens and candidate-locus studies. These and other data suggest that the genetic contribution to migraine is complex, multifactorial, and subject to significant modification by environmental factors.