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Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 × 10⁻⁹, odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 × 10⁻¹¹ (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 × 10⁻⁵, permuted threshold for genome-wide significance 7.7 × 10⁻⁵. To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.

Original publication

DOI

10.1038/ng.652

Type

Journal article

Journal

Nature genetics

Publication Date

10/2010

Volume

42

Pages

869 - 873

Addresses

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK. verneri.anttila@sanger.ac.uk

Keywords

International Headache Genetics Consortium, Lymphocytes, Cells, Cultured, Chromosomes, Human, Pair 8, Humans, Genetic Predisposition to Disease, Glutamate Carboxypeptidase II, Calcium-Binding Proteins, Cell Adhesion Molecules, Antigens, Surface, Case-Control Studies, Microsatellite Repeats, Genotype, Quantitative Trait Loci, Genome, Human, Female, Male, Migraine Disorders, Genome-Wide Association Study