title: Systematic re-evaluation of genes from candidate gene association studies in migraine using a large genome-wide association data set.
abstract: BACKGROUND
  Before the genome-wide association (GWA) era, many hypothesis-driven candidate gene association studies were performed that tested whether DNA variants in genes that had been selected based on prior knowledge about migraine pathophysiology were associated with migraine. Most studies involved small sample sets without robust replication, thereby making the risk of false-positive findings high. Genome-wide marker data of thousands of migraine patients and controls from the International Headache Genetics Consortium provide a unique opportunity to re-evaluate key findings from candidate gene association studies (and other non-GWA genetic studies) in a much larger data set.
  
  
  METHODS
  We selected 21 genes from published candidate gene association studies and six additional genes from other non-GWA genetic studies in migraine. Single nucleotide polymorphisms (SNPs) in these genes, as well as in the regions 500 kb up- and downstream, were inspected in IHGC GWAS data from 5175 clinic-based migraine patients with and without aura and 13,972 controls.
  
  
  RESULTS
  None of the SNPs in or near the 27 genes, including the SNPs that were previously found to be associated with migraine, reached the Bonferroni-corrected significance threshold; neither when analyzing all migraine patients together, nor when analyzing the migraine with and without aura patients or males and females separately.
  
  
  CONCLUSIONS
  The available migraine GWAS data provide no clear evidence for involvement of the previously reported most promising candidate genes in migraine.
authors: Department of Human Genetics, Leiden University Medical Center, the Netherlands.
authors: Boukje
authors: B
authors: de Vries
authors: Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, USA Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, USA Harvard Medical School, USA Stanley Center for Psychiatric Research, Broad Institute for Harvard and MIT, USA.
authors: Verneri
authors: V
authors: Anttila
authors: 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: Tobias
authors: T
authors: Freilinger
authors: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland Institute of Genetics, Folkhälsan Research Center, Finland.
authors: Maija
authors: M
authors: Wessman
authors: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland Institute of Genetics, Folkhälsan Research Center, Finland.
authors: Mari A
authors: MA
authors: Kaunisto
authors: Department of Neurology, Helsinki University Central Hospital, Finland.
authors: Mikko
authors: M
authors: Kallela
authors: Department of Neurology, Helsinki University Central Hospital, Finland.
authors: Ville
authors: V
authors: Artto
authors: Department of Human Genetics, Leiden University Medical Center, the Netherlands.
authors: Lisanne S
authors: LS
authors: Vijfhuizen
authors: Kiel Pain and Headache Center, Germany.
authors: Hartmut
authors: H
authors: Göbel
authors: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Germany Munich Cluster for Systems Neurology (SyNergy), Germany.
authors: Martin
authors: M
authors: Dichgans
authors: Institute of Human Genetics, University of Ulm, Germany.
authors: Christian
authors: C
authors: Kubisch
authors: Department of Neurology, Leiden University Medical Center, the Netherlands.
authors: Michel D
authors: MD
authors: Ferrari
authors: Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, USA Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, USA Stanley Center for Psychiatric Research, Broad Institute for Harvard and MIT, USA Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland Psychiatric and Neurodevelopmental Genetics Unit, Department of Medicine, Massachusetts General Hospital, USA Department of Neurology, Massachusetts General Hospital, USA.
authors: Aarno
authors: A
authors: Palotie
authors: Department of Neurology, Leiden University Medical Center, the Netherlands G.M.Terwindt@lumc.nl.
authors: Gisela M
authors: GM
authors: Terwindt
authors: Department of Human Genetics, Leiden University Medical Center, the Netherlands Department of Neurology, Leiden University Medical Center, the Netherlands.
authors: Arn Mjm
authors: AM
authors: van den Maagdenberg
mesh_terms: D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
keywords: GWAS data; Migraine; SNP; candidate genes