title: Candidate-gene association study searching for genetic factors involved in migraine chronification.
abstract: BACKGROUND
  Chronic migraine (CM) is at the severe end of the clinical migraine spectrum, but its genetic background is unknown. Our study searched for evidence that genetic factors are involved in the chronification process.
  
  
  METHODS
  We initially selected 144 single-nucleotide polymorphisms (SNPs) from 48 candidate genes, which we tested for association in two stages: The first stage encompassed 262 CM patients, the second investigated 226 patients with high-frequency migraine (HFM). Subsequently, SNPs with p values < 0.05 were forwarded to the replication stage containing 531 patients with CM or HFM.
  
  
  RESULTS
  Eight SNPs were significantly associated with CM and HFM in the two-stage phase. None survived replication in the third stage.
  
  
  CONCLUSIONS
  We present the first comprehensive genetic association study for migraine chronification. There were no significant findings. Future studies may benefit from larger, genome-wide data sets or should use other genetic approaches to identify genetic factors involved in migraine chronification.
authors.affiliation: Department of Neurology, Leiden University Medical Center (LUMC), the Netherlands Department of Psychiatry, Leiden University Medical Center (LUMC), the Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Louter
authors.affiliation: Headache and Neurological Pain Research Group, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona.
authors.forename: J
authors.initials: J
authors.lastname: Fernandez-Morales
authors.affiliation: Department of Human Genetics, Leiden University Medical Center (LUMC), the Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: de Vries
authors.affiliation: Department of Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, United Kingdom FORMI, Oslo University Hospital, Norway Department of Neurology, Oslo University Hospital, Norway Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: B
authors.initials: B
authors.lastname: Winsvold
authors.affiliation: 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 Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
authors.forename: V
authors.initials: V
authors.lastname: Anttila
authors.affiliation: Stroke Genetics and Pharmacogenetics, Fundació per la Docència i Recerca Mutua Terrassa, Spain Neurovascular Research Laboratory, Vall d'Hebron Institute of Research, Universidad Autonoma de Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Fernandez-Cadenas
authors.affiliation: Pediatric Neurology Research Group, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Vila-Pueyo
authors.affiliation: Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Spain Centre for Biomedical Network Research on Rare Diseases (CIBERER), Spain.
authors.forename: C
authors.initials: C
authors.lastname: Sintas
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, the Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Spain Centre for Biomedical Network Research on Rare Diseases (CIBERER), Spain Institute of Biomedicine of the University of Barcelona (IBUB), Spain.
authors.forename: B
authors.initials: B
authors.lastname: Cormand
authors.affiliation: Neurology Department, Hospital Universitari Vall d'Hebron (HUVH), Spain.
authors.forename: J
authors.initials: J
authors.lastname: Álvarez-Sabin
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Institute of Research, Universidad Autonoma de Barcelona, Spain Neurology Department, Hospital Universitari Vall d'Hebron (HUVH), Spain.
authors.forename: J
authors.initials: J
authors.lastname: Montaner
authors.affiliation: Department of Neurology, Leiden University Medical Center (LUMC), the Netherlands.
authors.forename: M D
authors.initials: MD
authors.lastname: Ferrari
authors.affiliation: Department of Neurology, Leiden University Medical Center (LUMC), the Netherlands Department of Human Genetics, Leiden University Medical Center (LUMC), the Netherlands.
authors.forename: Amjm
authors.initials: A
authors.lastname: van den Maagdenberg
authors.affiliation: Department of Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, United Kingdom 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 Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Palotie
authors.affiliation: FORMI, Oslo University Hospital, Norway Department of Neurology, Oslo University Hospital, Norway Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: J A
authors.initials: JA
authors.lastname: Zwart
authors.affiliation: Pediatric Neurology Research Group, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Macaya
authors.affiliation: Department of Neurology, Leiden University Medical Center (LUMC), the Netherlands.
authors.forename: G M
authors.initials: GM
authors.lastname: Terwindt
authors.affiliation: Headache and Neurological Pain Research Group, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona Neurology Department, Hospital Universitari Vall d'Hebron (HUVH), Spain ppozo@vhebron.net.
authors.forename: P
authors.initials: P
authors.lastname: Pozo-Rosich
mesh_terms: D002908:Chronic Disease; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
keywords: Chronic migraine; association studies; genetics; high-frequency migraine