Genome-wide meta-analysis identifies new susceptibility loci for migraine

被引：301

作者：

Anttila, Verneri ^{[1
,2
,3
,4
,5
]}

Winsvold, Bendik S. ^{[1
,6
,7
]}

Gormley, Padhraig ^{[1
]}

Kurth, Tobias ^{[4
,8
,9
,10
]}

Bettella, Francesco ^{[11
]}

McMahon, George ^{[12
]}

Kallela, Mikko ^{[13
]}

Malik, Rainer ^{[14
]}

de Vries, Boukje ^{[15
]}

Terwindt, Gisela ^{[16
]}

Medland, Sarah E. ^{[17
]}

Todt, Unda ^{[18
]}

McArdle, Wendy L. ^{[12
]}

Quaye, Lydia ^{[19
]}

Koiranen, Markku ^{[20
,21
]}

Ikram, M. Arfan ^{[22
,23
,24
]}

Lehtimaki, Terho ^{[25
,26
]}

Stam, Anine H. ^{[16
]}

Ligthart, Lannie ^{[27
,28
]}

Wedenoja, Juho ^{[29
]}

Dunham, Ian ^{[30
]}

Neale, Benjamin M. ^{[3
,4
,5
]}

Palta, Priit ^{[1
,2
]}

Hamalainen, Eija ^{[1
,2
]}

Schuerks, Markus ^{[31
]}

Rose, Lynda M. ^{[4
,10
]}

Buring, Julie E. ^{[4
,10
]}

Ridker, Paul M. ^{[4
,10
,32
]}

Steinberg, Stacy ^{[11
]}

Stefansson, Hreinn ^{[11
]}

Jakobsson, Finnbogi ^{[33
]}

Lawlor, Debbie A. ^{[12
]}

Evans, David M. ^{[12
]}

Ring, Susan M. ^{[12
]}

Farkkila, Markus ^{[13
]}

Artto, Ville ^{[13
]}

Kaunisto, Mari A. ^{[2
,34
]}

Freilinger, Tobias ^{[14
,35
]}

Schoenen, Jean ^{[36
,37
]}

Frants, Rune R. ^{[15
]}

Pelzer, Nadine ^{[16
]}

Weller, Claudia M. ^{[15
]}

Zielman, Ronald ^{[16
]}

Heath, Andrew C. ^{[38
]}

Madden, Pamela A. F. ^{[38
]}

Montgomery, Grant W. ^{[17
]}

Martin, Nicholas G. ^{[17
]}

Borck, Guntram ^{[18
]}

Goebel, Hartmut ^{[39
]}

Heinze, Axel ^{[39
]}

机构：

[1] Wellcome Trust Sanger Inst, Cambridge, England

[2] Univ Helsinki, FIMM, Helsinki, Finland

[3] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[4] Harvard Univ, Sch Med, Boston, MA USA

[5] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA

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

[7] Univ Oslo, Oslo, Norway

[8] INSERM, Neuroepidemiol U708, Bordeaux, France

[9] Univ Bordeaux, Bordeaux, France

[10] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA

[11] deCODE Genet, Reykjavik, Iceland

[12] Univ Bristol, Univ Bristol Med Res Council MRC Integrat Epidemi, Bristol, Avon, England

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

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

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

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

[17] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[18] Univ Ulm, Inst Human Genet, D-89069 Ulm, Germany

[19] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England

[20] Univ Oulu, Inst Hlth Sci, Oulu, Finland

[21] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland

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

[23] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands

[24] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands

[25] Fimlab Labs, Dept Clin Chem, Tampere, Finland

[26] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland

[27] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[28] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands

[29] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland

[30] European Mol Biol Lab, European Bioinformat Inst, Cambridge, England

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

[32] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA

[33] Landspitali Univ Hosp, Dept Neurol, Reykjavik, Iceland

[34] Folkhalsan Res Ctr, Helsinki, Finland

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

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

[37] Univ Liege, GIGA Neurosci, Liege, Belgium

[38] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

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

[40] Univ Hosp Oulu, Dept Clin Sci Obstet & Gynecol, Oulu, Finland

[41] Univ Oulu, Med Res Ctr, Oulu, Finland

[42] Natl Inst Hlth & Welf, Dept Children Young People & Families, Helsinki, Finland

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

[44] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany

[45] Univ Bonn, Inst Human Genet, Bonn, Germany

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

[47] Munich Cluster Syst Neurol SyNergy, Munich, Germany

[48] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

[49] Univ Kiel, Dept Internal Med 1, Kiel, Germany

[50] Helmholtz Ctr Munich, Inst Human Genet, Neuherberg, Germany

来源：

NATURE GENETICS | 2013年 / 45卷 / 08期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

TRANSFORMING-GROWTH-FACTOR; DOWN-REGULATION; ASSOCIATION; EXPRESSION; PROTEIN; FAMILY; MUTATIONS; LEWIS(X); GENES;

D O I：

10.1038/ng.2676

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P < 5 x 10(-8)). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.

引用

页码：912 / U255

页数：8

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