Involvement of astrocyte and oligodendrocyte gene sets in migraine

Else Eising; Christiaan de Leeuw; Josine L Min; Verneri Anttila; Mark Hg Verheijen; Gisela M Terwindt; Martin Dichgans; Tobias Freilinger; Christian Kubisch; International Headache Genetics Consortium; Michel D Ferrari; August B Smit; Boukje de Vries; Aarno Palotie; Arn Mjm van den Maagdenberg; Danielle Posthuma

doi:10.1177/0333102415618614

Involvement of astrocyte and oligodendrocyte gene sets in migraine

Cephalalgia. 2016 Jun;36(7):640-7. doi: 10.1177/0333102415618614. Epub 2015 Dec 7.

Authors

Else Eising¹, Christiaan de Leeuw², Josine L Min³, Verneri Anttila⁴, Mark Hg Verheijen⁵, Gisela M Terwindt⁶, Martin Dichgans⁷, Tobias Freilinger⁸, Christian Kubisch⁹; International Headache Genetics Consortium; Michel D Ferrari⁶, August B Smit⁵, Boukje de Vries¹, Aarno Palotie¹⁰, Arn Mjm van den Maagdenberg¹¹, Danielle Posthuma¹²

Affiliations

¹ Department of Human Genetics, Leiden University Medical Centre, The Netherlands.
² 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.
³ MRC Integrative Epidemiology Unit, University of Bristol, UK.
⁴ 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.
⁵ Department of Molecular and Cellular Neurobiology, Centre for Neurogenomics and Cognitive Research, Neuroscience, Campus Amsterdam, VU University, The Netherlands.
⁶ Department of Neurology, Leiden University Medical Centre, The Netherlands.
⁷ Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Germany Munich Cluster for Systems Neurology (SyNergy), Germany.
⁸ 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.
⁹ Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Germany.
¹⁰ 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.
¹¹ 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.
¹² 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.

PMID: 26646788
DOI: 10.1177/0333102415618614

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.

Discussion: 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.

Keywords: GWAS; Migraine; astrocytes; oligodendrocytes; pathway analysis; synapse.

MeSH terms

Adult
Astrocytes*
Female
Genome-Wide Association Study
Genotype
Humans
Male
Migraine Disorders / genetics*
Oligodendroglia*
Oligonucleotide Array Sequence Analysis