Hormonally modulated migraine is associated with single-nucleotide polymorphisms within genes involved in dopamine metabolism

Migraine is a complex trait in which multiple genetic loci, as well as environmental factors, likely contribute to its clinical manifestation. Many genetic associations reported in previous studies either have not been replicated to date or showed only marginal statistical significance, possibly due to the genetic heterogeneity of the common forms of migraine. One major phenotypic and possibly genetically identifiable migraine subgroup consists of women whose attacks are influenced by fluctuation in gonadal hormones. We hypothesized that for these women, the association between migraine attacks and the menstrual cycle might be attributable to an increased prevalence of genetic polymorphisms in the hypothalamic-pituitary-gonadal axis. We selected 21 such polymerphisms previously reported to be associated with the common forms of migraine and genotyped 1740 individuals (1132 migraineurs) to determine whether any of these selected polymorphisms occurred more frequently in females with hormonally modulated migraine. We were able to confirm the association of migraine with 3 genetic polymorphisms seen in previous studies (rs4680 [COMT], rs2283265 [DRD2], and rs7131056 [DRD2]). Interestingly, we found 2 additional genetic polymorphisms (rs2070762 [TH] and rs6356 [TH]) to be associated with migraine when defining the phenotype as hormonally modulated migraine.