title: Meta-analysis of genome-wide association for migraine in six population-based European cohorts.
abstract: Migraine is a common neurological disorder with a genetically complex background. This paper describes a meta-analysis of genome-wide association (GWA) studies on migraine, performed by the Dutch-Icelandic migraine genetics (DICE) consortium, which brings together six population-based European migraine cohorts with a total sample size of 10,980 individuals (2446 cases and 8534 controls). A total of 32 SNPs showed marginal evidence for association at a P-value<10(-5). The best result was obtained for SNP rs9908234, which had a P-value of 8.00 × 10(-8). This top SNP is located in the nerve growth factor receptor (NGFR) gene. However, this SNP did not replicate in three cohorts from the Netherlands and Australia. Of the other 31 SNPs, 18 SNPs were tested in two replication cohorts, but none replicated. In addition, we explored previously identified candidate genes in the meta-analysis data set. This revealed a modest gene-based significant association between migraine and the metadherin (MTDH) gene, previously identified in the first clinic-based GWA study (GWAS) for migraine (Bonferroni-corrected gene-based P-value=0.026). This finding is consistent with the involvement of the glutamate pathway in migraine. Additional research is necessary to further confirm the involvement of glutamate.
authors: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands. rsl.ligthart@psy.vu.nl
authors: Lannie
authors: L
authors: Ligthart
authors: Boukje
authors: B
authors: de Vries
authors: Albert V
authors: AV
authors: Smith
authors: M Arfan
authors: MA
authors: Ikram
authors: Najaf
authors: N
authors: Amin
authors: Jouke-Jan
authors: JJ
authors: Hottenga
authors: Stephany C
authors: SC
authors: Koelewijn
authors: V Mathijs
authors: VM
authors: Kattenberg
authors: Marleen H M
authors: MH
authors: de Moor
authors: A Cecile J W
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authors: Janssens
authors: Yurii S
authors: YS
authors: Aulchenko
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authors: Oostra
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authors: de Geus
authors: Johannes H
authors: JH
authors: Smit
authors: Frans G
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authors: Zitman
authors: André G
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authors: Uitterlinden
authors: Albert
authors: A
authors: Hofman
authors: Gonneke
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authors: Willemsen
authors: Dale R
authors: DR
authors: Nyholt
authors: Grant W
authors: GW
authors: Montgomery
authors: Gisela M
authors: GM
authors: Terwindt
authors: Vilmundur
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authors: Gudnason
authors: Brenda W J H
authors: BW
authors: Penninx
authors: Monique
authors: M
authors: Breteler
authors: Michel D
authors: MD
authors: Ferrari
authors: Lenore J
authors: LJ
authors: Launer
authors: Cornelia M
authors: CM
authors: van Duijn
authors: Arn M J M
authors: AM
authors: van den Maagdenberg
authors: Dorret I
authors: DI
authors: Boomsma
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D018698:Glutamic Acid / Q000096:biosynthesis; D007055:Iceland; D008565:Membrane Proteins; D008881:Migraine Disorders / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins; D017475:Receptors, Nerve Growth Factor / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D017475:Receptors, Nerve Growth Factor; D018698:Glutamic Acid