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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.

Original publication

DOI

10.1038/ng.2307

Type

Journal article

Journal

Nature genetics

Publication Date

10/06/2012

Volume

44

Pages

777 - 782

Addresses

Institute for Stroke and Dementia Research, Klinikum der Universität München, Munich, Germany.

Keywords

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