Genome-wide association study reveals three susceptibility loci for common migraine in the general population

Markus Schürks and colleagues report a genome-wide association study for common migraine. They identify three new susceptibility loci at PRDM16 , TRPM8 and LRP1 . Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic...

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Bibliographic Details
Published in:Nature genetics Vol. 43; no. 7; pp. 695 - 698
Main Authors: Chasman, Daniel I, Schürks, Markus, Anttila, Verneri, de Vries, Boukje, Schminke, Ulf, Launer, Lenore J, Terwindt, Gisela M, van den Maagdenberg, Arn M J M, Fendrich, Konstanze, Völzke, Henry, Ernst, Florian, Griffiths, Lyn R, Buring, Julie E, Kallela, Mikko, Freilinger, Tobias, Kubisch, Christian, Ridker, Paul M, Palotie, Aarno, Ferrari, Michel D, Hoffmann, Wolfgang, Zee, Robert Y L, Kurth, Tobias
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.07.2011
Nature Publishing Group
Subjects:
631/208/205/2138
631/208/727/2000
692/699/375/226/1654
692/700/478/174
Agriculture
Analysis
Animal Genetics and Genomics
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer Research
Case-Control Studies
Chromosomes, Human, Pair 1 - genetics
Chromosomes, Human, Pair 12 - genetics
Chromosomes, Human, Pair 2 - genetics
Cohort Studies
Confidence intervals
Epidemiology
Female
Fundamental and applied biological sciences. Psychology
Gene Function
Genealogy
Genetic aspects
Genetic Loci
Genetic Predisposition to Disease
Genetic susceptibility
Genetics
Genetics of eukaryotes. Biological and molecular evolution
Genome-Wide Association Study
Genomes
Headaches
Human Genetics
Humans
letter
Male
Medical sciences
Meta-analysis
Middle Aged
Migraine
Migraine without Aura - epidemiology
Migraine without Aura - genetics
Migraine without Aura - pathology
Neurology
Polymorphism, Single Nucleotide - genetics
Prognosis
Risk Factors
United States - epidemiology
Vascular diseases and vascular malformations of the nervous system
Womens health
United States
Germany
Vascular disease
Nervous system diseases
Pain
Migraine
Central nervous system disease
Cardiovascular disease
Locus
Cerebrovascular disease
Cerebral disorder
ISSN:1061-4036, 1546-1718, 1546-1718
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Summary:Markus Schürks and colleagues report a genome-wide association study for common migraine. They identify three new susceptibility loci at PRDM16 , TRPM8 and LRP1 . 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.
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on behalf of the International Headache Genetics Consortium (IHGC) (full list of consortium members appears in the supplement)
These authors contributed equally to the work.
ISSN:1061-4036
1546-1718
1546-1718
DOI:10.1038/ng.856