Journal
CEPHALALGIA
Volume 36, Issue 7, Pages 640-647Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0333102415618614
Keywords
Migraine; GWAS; pathway analysis; astrocytes; oligodendrocytes; synapse
Categories
Funding
- Netherlands Organization for Scientific Research (NWO) VIDI (ZonMw) [91711319]
- EUROHEADPAIN project [602633]
- Center for Medical Systems Biology (CMSB) in the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research (NGI/NWO) [050-060-409]
- Wellcome Trust [098051]
- Academy of Finland [251704, 139795]
- Academy of Finland, Center of Excellence in Complex Disease Genetics [213506, 129680]
- ENGAGE Consortium [HEALTH-F4-2007-201413]
- EU/SYNSYS-Synaptic Systems [242167]
- Sigrid Juselius Foundation
- Folkhalsan Research Foundation
- Medicinska Understodsforeningen Liv Halsa
- Helsinki University Central Hospital
- NWO Complexity project [645.000.003]
- NWO [480-05-003]
- Academy of Finland (AKA) [139795] Funding Source: Academy of Finland (AKA)
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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.
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