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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Vydané v:	Nature genetics Ročník 43; číslo 7; s. 695 - 698
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	New York Nature Publishing Group US 01.07.2011 Nature Publishing Group
Predmet:	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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Shrnutí:	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.
Bibliografia:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 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