title: Involvement of astrocyte and oligodendrocyte gene sets in migraine.
abstract: BACKGROUND
  Migraine is a common episodic brain disorder characterized by recurrent attacks of severe unilateral headache and additional neurological symptoms. Two main migraine types can be distinguished based on the presence of aura symptoms that can accompany the headache: migraine with aura and migraine without aura. Multiple genetic and environmental factors confer disease susceptibility. Recent genome-wide association studies (GWAS) indicate that migraine susceptibility genes are involved in various pathways, including neurotransmission, which have already been implicated in genetic studies of monogenic familial hemiplegic migraine, a subtype of migraine with aura.
  
  
  METHODS
  To further explore the genetic background of migraine, we performed a gene set analysis of migraine GWAS data of 4954 clinic-based patients with migraine, as well as 13,390 controls. Curated sets of synaptic genes and sets of genes predominantly expressed in three glial cell types (astrocytes, microglia and oligodendrocytes) were investigated.
  
  
  CONCLUSIONS
  Our results show that gene sets containing astrocyte- and oligodendrocyte-related genes are associated with migraine, which is especially true for gene sets involved in protein modification and signal transduction. Observed differences between migraine with aura and migraine without aura indicate that both migraine types, at least in part, seem to have a different genetic background.
authors.affiliation: Department of Human Genetics, Leiden University Medical Centre, The Netherlands.
authors.forename: Else
authors.initials: E
authors.lastname: Eising
authors.affiliation: Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, The Netherlands Institute for Computing and Information Sciences, Radboud University, The Netherlands.
authors.forename: Christiaan
authors.initials: C
authors.lastname: de Leeuw
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, UK.
authors.forename: Josine L
authors.initials: JL
authors.lastname: Min
authors.affiliation: Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, USA Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, USA Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, USA.
authors.forename: Verneri
authors.initials: V
authors.lastname: Anttila
authors.affiliation: Department of Molecular and Cellular Neurobiology, Centre for Neurogenomics and Cognitive Research, Neuroscience, Campus Amsterdam, VU University, The Netherlands.
authors.forename: Mark Hg
authors.initials: MH
authors.lastname: Verheijen
authors.affiliation: Department of Neurology, Leiden University Medical Centre, The Netherlands.
authors.forename: Gisela M
authors.initials: GM
authors.lastname: Terwindt
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Germany Munich Cluster for Systems Neurology (SyNergy), Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Germany Department of Neurology and Epileptology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Freilinger
authors.affiliation: Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kubisch
authors.affiliation: Department of Neurology, Leiden University Medical Centre, The Netherlands.
authors.forename: Michel D
authors.initials: MD
authors.lastname: Ferrari
authors.affiliation: Department of Molecular and Cellular Neurobiology, Centre for Neurogenomics and Cognitive Research, Neuroscience, Campus Amsterdam, VU University, The Netherlands.
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.affiliation: Department of Human Genetics, Leiden University Medical Centre, The Netherlands.
authors.forename: Boukje
authors.initials: B
authors.lastname: de Vries
authors.affiliation: Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, USA Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, USA Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, USA Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, UK Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.affiliation: Department of Human Genetics, Leiden University Medical Centre, The Netherlands Department of Neurology, Leiden University Medical Centre, The Netherlands A.M.J.M.van_den_Maagdenberg@lumc.nl.
authors.forename: Arn Mjm
authors.initials: AM
authors.lastname: van den Maagdenberg
authors.affiliation: Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, The Netherlands Department of Clinical Genetics, VU University Medical Centre, The Netherlands.
authors.forename: Danielle
authors.initials: D
authors.lastname: Posthuma
mesh_terms: D000328:Adult; D001253:Astrocytes; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000235:genetics*; D009836:Oligodendroglia; D020411:Oligonucleotide Array Sequence Analysis
keywords: GWAS; Migraine; astrocytes; oligodendrocytes; pathway analysis; synapse