EVIDENCE FOR AN X-LINKED GENETIC COMPONENT IN FAMILIAL TYPICAL MIGRAINE

Migraine is a common complex disorder that shows strong familial aggre gation. There is; a general increased prevalence of migraine in female s compared with males, with recent studies indicating that migraine af fects 18% of females compared with 6% of males. This females among mig raine sufferers evidence of an increased risk of migraine in first deg ree relatives of male probands but not in relatives of female probands bi suggests the possibility of an X-linked dominant gene. We report h ere the localization of a typical migraine I susceptibility locus to t he X chromosome. Of three large multigenerational migraine pedigrees t wo families showed significant excess allele sharing to Xq markers (P = 0.031 and P = 0.012). Overall analysis of data from all three pedigr ees gave significant evidence in support of linkage and heterogeneity (HLOD = 3.1). These findings provide conclusive evidence that familial typical migraine is a heterogeneous disorder. We suggest that the loc alization of a migraine susceptibility locus to the X chromosome could in part explain the increased risk of migraine in relatives of male p robands and may be involved in the increased female prevalence of this disorder.