Genome-wide association analysis identifies susceptibility loci for migraine without aura

Nat Genet. 2012 Jun 10;44(7):777-82. doi: 10.1038/ng.2307.

Abstract

Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 × 10(-4); combined P = 7.06 × 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 × 10(-4); combined P = 1.17 × 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10(-8) and P = 0.02; combined P = 3.86 × 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study / methods
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1 / genetics
  • MADS Domain Proteins / genetics
  • MEF2 Transcription Factors
  • Male
  • Microfilament Proteins / genetics
  • Migraine without Aura / genetics*
  • Myogenic Regulatory Factors / genetics
  • Polymorphism, Single Nucleotide
  • Protein-Serine-Threonine Kinases / genetics
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • TRPM Cation Channels / genetics

Substances

  • LRP1 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-1
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • MEF2D protein, human
  • Microfilament Proteins
  • Myogenic Regulatory Factors
  • Phactr-1 protein, human
  • Receptors, Transforming Growth Factor beta
  • TRPM Cation Channels
  • TRPM8 protein, human
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II