title: Genome-wide association study reveals three susceptibility loci for common migraine in the general population.
abstract: Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 × 10(-6)) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 × 10(-9); rs10166942, OR = 0.85, P = 5.5 × 10(-12); and rs11172113, OR = 0.90, P = 4.3 × 10(-9)). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology.
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.forename: Markus
authors.initials: M
authors.lastname: Schürks
authors.forename: Verneri
authors.initials: V
authors.lastname: Anttila
authors.forename: Boukje
authors.initials: B
authors.lastname: de Vries
authors.forename: Ulf
authors.initials: U
authors.lastname: Schminke
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.forename: Gisela M
authors.initials: GM
authors.lastname: Terwindt
authors.forename: Arn M J M
authors.initials: AM
authors.lastname: van den Maagdenberg
authors.forename: Konstanze
authors.initials: K
authors.lastname: Fendrich
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.forename: Florian
authors.initials: F
authors.lastname: Ernst
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.forename: Mikko
authors.initials: M
authors.lastname: Kallela
authors.forename: Tobias
authors.initials: T
authors.lastname: Freilinger
authors.forename: Christian
authors.initials: C
authors.lastname: Kubisch
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Michel D
authors.initials: MD
authors.lastname: Ferrari
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hoffmann
authors.forename: Robert Y L
authors.initials: RY
authors.lastname: Zee
authors.forename: Tobias
authors.initials: T
authors.lastname: Kurth
mesh_terms: D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020326:Migraine without Aura / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012307:Risk Factors; D014481:United States / Q000453:epidemiology