Migraine is a common, chronic neurovascular disorder caused by a complex interaction
between genetic and environmental risk factors. In the last two decades, molecular genetics
of migraine have been intensively investigated. In a few cases, migraine is transmitted as a
monogenic disorder, and the disease phenotype cosegregates with mutations in different genes
like CACNA1A, ATP1A2, SCN1A, KCNK18, and NOTCH3. In the common forms of migraine,
candidate genes as well as genome-wide association studies have shown that a large number of
genetic variants may increase the risk of developing migraine. At present, few studies investigated
the genotype-phenotype correlation in patients with migraine. The purpose of this review
was to discuss recent studies investigating the relationship between different genetic variants
and the clinical characteristics of migraine. Analysis of genotype-phenotype correlations in
migraineurs is complicated by several confounding factors and, to date, only polymorphisms
of the MTHFR gene have been shown to have an effect on migraine phenotype. Additional
genomic studies and network analyses are needed to clarify the complex pathways underlying
migraine and its clinical phenotypes.
Editing GWAS: experimental approaches to dissect and exploit disease-associated genetic variation