title: The association between candidate migraine susceptibility loci and severe migraine phenotype in a clinical sample.
abstract: BACKGROUND
  The objective of the study was to follow up and to test whether 12 previously identified migraine-associated single nucleotide polymorphisms were associated as risk factors and/or modifying factors for severe migraine traits in a Danish clinic-based population.
  
  
  METHODS
  Semi-structured migraine interviews, blood sampling and genotyping were performed on 1806 unrelated migraineurs recruited from the Danish Headache Center. Genotyping was also performed on a control group of 6415 people with no history of migraine. Association analyses were carried out using logistic regression and odds ratios were calculated assuming an additive model for risk. The proxies for severe migraine traits (early onset of migraine; many lifetime attacks, prolonged migraine and tendency to chronification of migraine) were tested against the 12 single nucleotide polymorphisms and a combined genetic score in both a case-control and case-only logistic regression model.
  
  
  RESULTS
  We successfully replicated five out of the 12 previously reported loci and confirmed the same direction of effects for all the 12 single nucleotide polymorphisms. In line with the recently published genome-wide association meta-analysis, the associations were significant for all migraine and migraine without aura but not for migraine with typical aura. Two single nucleotide polymorphisms (rs2274316 and rs11172113) conferred risk of many lifetime attacks inthe case-control analysis. In the case-only analysis, only three single nucleotide polymorphisms showed nominal association with many lifetime attacks and prolonged migraine attacks.
  
  
  CONCLUSIONS
  Our study supports previously reported findings on the association of several single nucleotide polymorphisms with migraine. It also suggests that the migraine susceptibility loci may be risk factors for severe migraine traits.
authors: The Danish Headache Center, Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
authors: Ann-Louise
authors: AL
authors: Esserlind
authors: The Danish Headache Center, Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
authors: Anne Francke
authors: AF
authors: Christensen
authors: deCODE Genetics, Iceland.
authors: Stacy
authors: S
authors: Steinberg
authors: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors: Niels
authors: N
authors: Grarup
authors: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors: Oluf
authors: O
authors: Pedersen
authors: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark Faculty of Health Sciences, University of Southern Denmark, Denmark.
authors: Torben
authors: T
authors: Hansen
authors: Institute of Biological Psychiatry, MHC Sct. Hans, Copenhagen Mental Health Services; Department of Clinical Medicine, University of Copenhagen; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
authors: Thomas
authors: T
authors: Werge
authors: Institute of Biological Psychiatry, MHC Sct. Hans, Copenhagen Mental Health Services; Department of Clinical Medicine, University of Copenhagen; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
authors: Thomas Folkmann
authors: TF
authors: Hansen
authors: Research Centre for Prevention and Health, the Capital Region of Denmark, Denmark.
authors: Lise Lotte N
authors: LL
authors: Husemoen
authors: Research Centre for Prevention and Health, the Capital Region of Denmark, Denmark Department of Clinical Experimental Research, Glostrup University Hospital, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors: Allan
authors: A
authors: Linneberg
authors: Department of Public Health, University of Copenhagen, Denmark.
authors: Esben
authors: E
authors: Budtz-Jorgensen
authors: The Danish Headache Center, Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
authors: Maria Lurenda
authors: ML
authors: Westergaard
authors: deCODE Genetics, Iceland.
authors: Hreinn
authors: H
authors: Stefansson
authors: The Danish Headache Center, Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark jeol@regionh.dk.
authors: Jes
authors: J
authors: Olesen
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
keywords: Migraine; clinic-based sample; genetics; genome-wide association studies; replication; susceptibility loci