Genome-wide association analysis identifies susceptibility loci for migraine without aura

被引：257

作者：

Freilinger, Tobias ^{[2
,3
]}

Anttila, Verneri ^{[1
,4
]}

de Vries, Boukje ^{[5
]}

Malik, Rainer ^{[2
]}

Kallela, Mikko ^{[6
]}

Terwindt, Gisela M. ^{[7
]}

Pozo-Rosich, Patricia ^{[8
,9
]}

Winsvold, Bendik ^{[1
,10
,11
]}

Nyholt, Dale R. ^{[12
]}

van Oosterhout, Willebrordus P. J. ^{[7
]}

Artto, Ville ^{[6
]}

Todt, Unda ^{[13
]}

Hamalainen, Eija ^{[1
,4
]}

Fernandez-Morales, Jessica ^{[1
,9
]}

Louter, Mark A. ^{[7
,14
]}

Kaunisto, Mari A. ^{[4
,15
]}

Schoenen, Jean ^{[16
,17
]}

Raitakari, Olli ^{[18
,19
]}

Lehtimaki, Terho ^{[20
,21
]}

Vila-Pueyo, Marta ^{[22
]}

Goebel, Hartmut ^{[23
]}

Wichmann, Erich ^{[24
]}

Sintas, Celia ^{[25
,26
]}

Uitterlinden, Andre G. ^{[27
]}

Hofman, Albert ^{[28
]}

Rivadeneira, Fernando ^{[27
,28
]}

Heinze, Axel ^{[23
]}

Tronvik, Erling ^{[29
]}

van Duijn, Cornelia M. ^{[28
]}

Kaprio, Jaakko ^{[4
,30
,31
]}

Cormand, Bru ^{[26
,32
]}

Wessman, Maija ^{[4
,15
]}

Frants, Rune R. ^{[5
]}

Meitinger, Thomas ^{[33
,34
]}

Mueller-Myhsok, Bertram ^{[35
]}

Zwart, John-Anker ^{[10
,11
]}

Farkkila, Markus ^{[6
]}

Macaya, Alfons ^{[22
]}

Ferrari, Michel D. ^{[7
]}

Kubisch, Christian ^{[13
]}

Palotie, Aarno ^{[1
,4
,36
,37
,38
]}

Dichgans, Martin ^{[2
]}

van den Maagdenberg, Arn M. J. M. ^{[5
,7
]}

机构：

[1] Wellcome Trust Sanger Inst, Cambridge, England

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

[3] Klinikum Univ Munchen, Dept Neurol, Munich, Germany

[4] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

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

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

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

[8] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Dept Neurol, E-08193 Barcelona, Spain

[9] Univ Autonoma Barcelona, Vall dHebron Res Inst, Headache Res Grp, E-08193 Barcelona, Spain

[10] Oslo Univ Hosp, Dept Neurol, Oslo, Norway

[11] Univ Oslo, Oslo, Norway

[12] Queensland Inst Med Res, Neurogenet Lab, Brisbane, Qld 4006, Australia

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

[14] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands

[15] Folkhalsan Res Ctr, Helsinki, Finland

[16] Univ Liege, Headache Res Unit, Dept Neurol, Liege, Belgium

[17] Univ Liege, Headache Res Unit, Grp Interdisciplinaire Genoprote Appl GIGA Neuros, Liege, Belgium

[18] Univ Turku, Dept Clin Psychol, Turku, Finland

[19] Turku Univ, Cent Hosp, Turku, Finland

[20] Tampere Univ Hosp, Dept Clin Chem, Tampere, Finland

[21] Univ Tampere, FIN-33101 Tampere, Finland

[22] Univ Autonoma Barcelona, Vall dHebron Res Inst, Pediat Neurol Res Grp, E-08193 Barcelona, Spain

[23] Kiel Pain & Headache Ctr, Kiel, Germany

[24] Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany

[25] Univ Barcelona, Dept Genet, Barcelona, Spain

[26] Biomed Network Res Ctr Rare Dis CIBERER, Barcelona, Spain

[27] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[28] Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands

[29] Norwegian Univ Sci & Technol, Dept Neurosci, N-7034 Trondheim, Norway

[30] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland

[31] Natl Inst Hlth & Welf, Dept Mental Hlth & Alcohol Res, Helsinki, Finland

[32] Univ Barcelona, Inst Biomed, Barcelona, Spain

[33] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany

[34] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80804 Munich, Germany

[35] Max Planck Inst Psychiat, D-80804 Munich, Germany

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

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

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

来源：

NATURE GENETICS | 2012年 / 44卷 / 07期

基金：

芬兰科学院; 英国医学研究理事会; 澳大利亚研究理事会; 英国惠康基金;

关键词：

GENERAL-POPULATION; NEUROPATHIC PAIN; RECEPTOR; METAANALYSIS; EXPRESSION; COMMON; MEF2; HEADACHE; PROTEIN; FAMILY;

D O I：

10.1038/ng.2307

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 x 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 x 10(-4); combined P = 7.06 x 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 x 10(-4); combined P = 1.17 x 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 x 10(-8) and P = 0.02; combined P = 3.86 x 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.

引用

页码：777 / U205

页数：8

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