title: Pearls and pitfalls in genetic studies of migraine.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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 mechanisms involved.
  
  
  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.
authors.affiliation: Department of Human Genetics, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
authors.forename: Else
authors.initials: E
authors.lastname: Eising
authors.forename: Boukje
authors.initials: B
authors.lastname: de Vries
authors.forename: Michel D
authors.initials: MD
authors.lastname: Ferrari
authors.forename: Gisela M
authors.initials: GM
authors.lastname: Terwindt
authors.forename: Arn M J M
authors.initials: AM
authors.lastname: van den Maagdenberg
mesh_terms: D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D036281:Genetic Research; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008881:Migraine Disorders / Q000453:epidemiology* / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence
chemical_list: D005819:Genetic Markers; D009419:Nerve Tissue Proteins
keywords: Migraine; association; gene; genome-wide; linkage; next-generation sequencing