Pearls and pitfalls in genetic studies of migraine
Eising, E., De Vries, B., Ferrari, M. D., Terwindt, G. M., & Van Den Maagdenberg, A. M. J. M.
Pearls and pitfalls in genetic studies of migraine. Cephalalgia, 33
(8), 614-625. doi:10.1177/0333102413484988.
Purpose of review: Migraine is a prevalent neurovascular brain disorder with a strong genetic component, and different
methodological approaches have been implemented to identify the genes involved. This review focuses on pearls and
pitfalls of these approaches and genetic findings in migraine.
Summary: Common forms of migraine (i.e. migraine with and without aura) are thought to have a polygenic make-up,
whereas rare familial hemiplegic migraine (FHM) presents with a monogenic pattern of inheritance. Until a few years ago
only studies in FHM yielded causal genes, which were identified by a classical linkage analysis approach. Functional
analyses of FHM gene mutations in cellular and transgenic animal models suggest abnormal glutamatergic neurotransmission
as a possible key disease mechanism. Recently, a number of genes were discovered for the common forms
of migraine using a genome-wide association (GWA) approach, which sheds first light on the pathophysiological
Conclusions: Novel technological strategies such as next-generation sequencing, which can be implemented in future
genetic migraine research, may aid the identification of novel FHM genes and promote the search for the missing
heritability of common migraine.