Involvement of astrocyte and oligodendrocyte gene sets in migraine

Author:

Eising Else1,de Leeuw Christiaan23,Min Josine L4,Anttila Verneri567,Verheijen Mark HG8,Terwindt Gisela M9,Dichgans Martin1011,Freilinger Tobias1012,Kubisch Christian13,Ferrari Michel D9,Smit August B8,de Vries Boukje1,Palotie Aarno5671415,van den Maagdenberg Arn MJM19,Posthuma Danielle216,

Affiliation:

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

3. Institute for Computing and Information Sciences, Radboud University, The Netherlands

4. MRC Integrative Epidemiology Unit, University of Bristol, UK

5. Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, USA

6. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, USA

7. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, USA

8. Department of Molecular and Cellular Neurobiology, Centre for Neurogenomics and Cognitive Research, Neuroscience, Campus Amsterdam, VU University, The Netherlands

9. Department of Neurology, Leiden University Medical Centre, The Netherlands

10. Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Germany

11. Munich Cluster for Systems Neurology (SyNergy), Germany

12. Department of Neurology and Epileptology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany

13. Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Germany

14. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, UK

15. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland

16. Department of Clinical Genetics, VU University Medical Centre, The Netherlands

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.

Publisher

SAGE Publications

Subject

Clinical Neurology,General Medicine

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