Lancet publishes comprehensive review on migraine

A review paper in the Lancet discusses diagnosis, the genetic background of migraine, and new phenotyping strategies that might help in the search for genes.Migraine affects about 15% of people in developed countries and is three times more common in women than in men. Previous research shows that patients have a median of one attack per month and 25% have at least two attacks per month. Patients with more than one attack per month are at increased risk of brain lesions.Careful diagnosis and subclassification are essential for genetic studies of complex diseases and can be especially demanding when no laboratory or other diagnostic test is available, as is the case with migraine, Dr Maija Wessman (Department of Neurology, University medical Centre, Leiden, Netherlands) write. They remark that the difficulty in uncovering gene variants associated with migraine has stimulated a search for new research strategies.Wessman et al. go on to discuss the diagnosis, clinical spectrum cormobidity and genetic mechanisms relating to migraine. They note that the rare mendelian form of migraine (FHM) is the most successful model for the identification of migraine-associated cellular mechanisms."These studies have pinpointed channelopathies, although direct evidence for the involvement of the genes in common forms of migraine has not been found," they write. They suggest that the situation with migraine might resemble those of hypertension and epilepsy in which several mendelian traits have been identified: in hypertension they all interfere with the normal function of the critical molecules involved in the regulation of the salt balance of the body by the kidneys and in epilepsy they affect ion channels of the CNS. "However, the identification of genes predisposing to more common forms of these traits has been less successful. The many linkage peaks detected in genome-wide scans in both migraine and hypertension support the hypothesis that these traits are heterogeneous and on a family level include some relatively strongly penetrant variants, which on a population level might have a relatively modest effect."If this hypothesis is even partially correct, they write, one could speculate that the phenotypes commonly used (migraine with and migraine without aura) are not optimum for genetic studies. Latent class and trait component analyses might help to reclassify the phenotypes to facilitate identification of common variants predisposing to headache disorders, they conclude. Reference...