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

被引：301

作者：

Chasman, Daniel I. ^{[1
,2
]}

Schuerks, Markus ^{[1
,3
]}

Anttila, Verneri ^{[4
,5
]}

de Vries, Boukje ^{[6
]}

Schminke, Ulf ^{[7
]}

Launer, Lenore J. ^{[8
]}

Terwindt, Gisela M. ^{[9
]}

van den Maagdenberg, Arn M. J. M. ^{[6
,9
]}

Fendrich, Konstanze ^{[10
]}

Voelzke, Henry ^{[11
]}

Ernst, Florian ^{[12
]}

Griffiths, Lyn R. ^{[13
]}

Buring, Julie E. ^{[1
]}

Kallela, Mikko ^{[14
]}

Freilinger, Tobias ^{[15
,16
]}

Kubisch, Christian ^{[17
]}

Ridker, Paul M. ^{[1
,2
]}

Palotie, Aarno ^{[4
,5
,18
,19
,20
]}

Ferrari, Michel D. ^{[9
]}

Hoffmann, Wolfgang ^{[10
]}

Zee, Robert Y. L. ^{[1
]}

Kurth, Tobias ^{[1
,21
,22
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA

[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Donald W Reynolds Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA

[3] Univ Hosp Essen, Dept Neurol, Essen, Germany

[4] Wellcome Trust Sanger Inst, Cambridge, England

[5] Univ Helsinki, FIMM, Helsinki, Finland

[6] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands

[7] Ernst Moritz Arndt Univ Greifswald, Dept Neurol, Greifswald, Germany

[8] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA

[9] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands

[10] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Sect Epidemiol Hlth Care & Community Hlth, Greifswald, Germany

[11] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Sect Clin Epidemiol Res, Greifswald, Germany

[12] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[13] Griffith Univ, Griffith Hlth Inst, Genom Res Ctr, Gold Coast, Qld, Australia

[14] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland

[15] Univ Munich, Klinikum Grosshadern, Dept Neurol, Munich, Germany

[16] Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany

[17] Univ Ulm, Inst Human Genet, Ulm, Germany

[18] Univ Helsinki, Dept Med Genet, Helsinki, Finland

[19] Univ Helsinki, Cent Hosp, Dept Med Genet, Helsinki, Finland

[20] Broad Inst MIT & Harvard, Boston, MA USA

[21] INSERM, Neuroepidemiol U708, Paris, France

[22] Univ Paris 06, F-75005 Paris, France

来源：

NATURE GENETICS | 2011年 / 43卷 / 07期

基金：

英国惠康基金; 芬兰科学院;

关键词：

RECEPTOR; COHORT; HEALTH; TOOL;

D O I：

10.1038/ng.856

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 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 x 10(-9); rs10166942, OR = 0.85, P = 5.5 x 10(-12); and rs11172113, OR = 0.90, P = 4.3 x 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.

引用

页码：695 / U116

页数：5

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