Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

被引：465

作者：

Gormley, Padhraig ^{[1
,2
,3
,4
,5
]}

Anttila, Verneri ^{[2
,3
,4
,6
]}

Winsvold, Bendik S. ^{[7
,8
,9
]}

Palta, Priit ^{[10
]}

Esko, Tonu ^{[3
,11
,12
]}

Pers, Tune H. ^{[3
,12
,13
,14
]}

Farh, Kai-How ^{[2
,3
,6
,15
]}

Cuenca-Leon, Ester ^{[1
,2
,3
,4
,16
]}

Muona, Mikko ^{[10
,17
,18
,19
]}

Furlotte, Nicholas A. ^{[20
]}

Kurth, Tobias ^{[21
,22
]}

Ingason, Andres ^{[23
]}

McMahon, George ^{[24
]}

Ligthart, Lannie ^{[25
]}

Terwindt, Gisela M. ^{[26
]}

Kallela, Mikko ^{[27
]}

Freilinger, Tobias M. ^{[28
,29
]}

Ran, Caroline ^{[30
]}

Gordon, Scott G. ^{[31
]}

Stam, Anine H. ^{[26
]}

Steinberg, Stacy ^{[23
]}

Borck, Guntram ^{[32
]}

Koiranen, Markku ^{[33
]}

Quaye, Lydia ^{[34
]}

Adams, Hieab H. H.

Lehtimaki, Terho

Sarin, Antti-Pekka ^{[10
]}

Wedenoja, Juho ^{[37
]}

Hinds, David A. ^{[20
]}

Buring, Julie E. ^{[22
,38
]}

Schurks, Markus ^{[39
]}

Ridker, Paul M. ^{[22
,38
]}

Hrafnsdottir, Maria Gudlaug ^{[40
]}

Stefansson, Hreinn ^{[23
]}

Ring, Susan M. ^{[24
]}

Hottenga, Jouke-Jan ^{[25
]}

Penninx, Brenda W. J. H. ^{[41
]}

Farkkila, Markus ^{[27
]}

Artto, Ville ^{[27
]}

Kaunisto, Mari ^{[10
]}

Vepsalainen, Salli ^{[27
]}

Malik, Rainer ^{[29
]}

Heath, Andrew C. ^{[42
]}

Madden, Pamela A. F. ^{[42
]}

Martin, Nicholas G. ^{[31
]}

Montgomery, Grant W. ^{[31
]}

Kurki, Mitja I. ^{[1
,2
,3
,4
,10
,43
]}

Kals, Mart ^{[11
]}

Magi, Reedik ^{[11
]}

Parn, Kalle ^{[11
]}

机构：

[1] Massachusetts Gen Hosp, Psychiat & Neurodevelopmental Genet Unit, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA 02138 USA

[3] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA 02139 USA

[4] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA

[5] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, Cambs, England

[6] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[7] Oslo Univ Hosp, FORMI, Oslo, Norway

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

[9] Univ Oslo, Inst Clin Med, Oslo, Norway

[10] Univ Helsinki, FIMM, Helsinki, Finland

[11] Univ Tartu, Estonian Genome Ctr, Tartu, Estonia

[12] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA

[13] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark

[14] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

[15] Illumina, San Diego, CA USA

[16] Vall dHebron Res Inst, Pediat Neurol, Barcelona, Spain

[17] Folkhalsan Inst Genet, Helsinki, Finland

[18] Univ Helsinki, Ctr Neurosci, Helsinki, Finland

[19] Univ Helsinki, Res Programs Unit, Mol Neurol Res Program, Helsinki, Finland

[20] 23andMe Inc, Mountain View, CA USA

[21] Charite, Inst Publ Hlth, D-13353 Berlin, Germany

[22] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA

[23] deCODE Genet, Reykjavik, Iceland

[24] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England

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

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

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

[28] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurol & Epileptol, Tubingen, Germany

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

[30] Karolinska Inst, Dept Neurosci, Stockholm, Sweden

[31] QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia

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

[33] Univ Oulu, Ctr Life Course Epidemiol & Syst Med, Oulu, Finland

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

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

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

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

[38] Harvard Med Sch, Boston, MA USA

[39] Univ Duisburg Essen, Dept Neurol, Essen, Germany

[40] Landspitali Univ Hosp, Reykjavik, Iceland

[41] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands

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

[43] Kuopio Univ Hosp, Dept Neurosurg, SF-70210 Kuopio, Finland

[44] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[45] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford, England

[46] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England

[47] John Radcliffe Hosp, Oxford Headache Ctr, Oxford, England

[48] Max Planck Inst Psychiat, Munich, Germany

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

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

来源：

NATURE GENETICS | 2016年 / 48卷 / 08期

关键词：

GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; FAMILIAL HEMIPLEGIC MIGRAINE; GENE-EXPRESSION; SPREADING DEPRESSION; QUALITY-CONTROL; MOUSE MODELS; NITRIC-OXIDE; MUTATION; CALCIUM;

D O I：

10.1038/ng.3598

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association ( GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms ( SNPs) significantly associated with migraine risk ( P < 5 x 10(-8)) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.

引用

页码：856 / +

页数：14

共 91 条

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共 91 条

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Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

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Wilson, Richard K. ;

Gibbs, Richard A. ;

Dinh, Huyen ;

Kovar, Christie ;

Lee, Sandra ;

Lewis, Lora ;

Muzny, Donna ;

Reid, Jeff ;

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Wang, Jun ;

Fang, Xiaodong ;

Guo, Xiaosen ;

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de Bakker, Paul I. W. ;

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Inouye, Michael ;

Jia, Xiaoming ;

Palotie, Aarno ;

Parkin, Melissa ;

Whittaker, Pamela ;

Chang, Kyle ;

Hawes, Alicia ;

Lewis, Lora R. ;

Ren, Yanru ;

Wheeler, David ;

Muzny, Donna Marie ;

Barnes, Chris ;

Darvishi, Katayoon ;

Hurles, Matthew ;

Korn, Joshua M. ;

Kristiansson, Kati ;

Lee, Charles ;

McCarroll, Steven A. ;

Nemesh, James ;

Keinan, Alon ;

Montgomery, Stephen B. ;

Pollack, Samuela ;

Price, Alkes L. ;

Soranzo, Nicole ;

Gonzaga-Jauregui, Claudia ;

Anttila, Verneri ;

Brodeur, Wendy ;

Daly, Mark J. ;

Leslie, Stephen ;

McVean, Gil ;

Moutsianas, Loukas ;

Nguyen, Huy ;

Zhang, Qingrun ;

Ghori, Mohammed J. R. ;

McGinnis, Ralph ;

McLaren, William ;

Takeuchi, Fumihiko ;

Grossman, Sharon R. .

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Anttila, Verneri ;

Winsvold, Bendik S. ;

Gormley, Padhraig ;

Kurth, Tobias ;

Bettella, Francesco ;

McMahon, George ;

Kallela, Mikko ;

Malik, Rainer ;

de Vries, Boukje ;

Terwindt, Gisela ;

Medland, Sarah E. ;

Todt, Unda ;

McArdle, Wendy L. ;

Quaye, Lydia ;

Koiranen, Markku ;

Ikram, M. Arfan ;

Lehtimaki, Terho ;

Stam, Anine H. ;

Ligthart, Lannie ;

Wedenoja, Juho ;

Dunham, Ian ;

Neale, Benjamin M. ;

Palta, Priit ;

Hamalainen, Eija ;

Schuerks, Markus ;

Rose, Lynda M. ;

Buring, Julie E. ;

Ridker, Paul M. ;

Steinberg, Stacy ;

Stefansson, Hreinn ;

Jakobsson, Finnbogi ;

Lawlor, Debbie A. ;

Evans, David M. ;

Ring, Susan M. ;

Farkkila, Markus ;

Artto, Ville ;

Kaunisto, Mari A. ;

Freilinger, Tobias ;

Schoenen, Jean ;

Frants, Rune R. ;

Pelzer, Nadine ;

Weller, Claudia M. ;

Zielman, Ronald ;

Heath, Andrew C. ;

Madden, Pamela A. F. ;

Montgomery, Grant W. ;

Martin, Nicholas G. ;

Borck, Guntram ;

Goebel, Hartmut ;

Heinze, Axel .

NATURE GENETICS, 2013, 45 (08) :912-U255

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Anttila, Verneri ;

Stefansson, Hreinn ;

Kallela, Mikko ;

Todt, Unda ;

Terwindt, Gisela M. ;

Calafato, M. Stella ;

Nyholt, Dale R. ;

Dimas, Antigone S. ;

Freilinger, Tobias ;

Mueller-Myhsok, Bertram ;

Artto, Ville ;

Inouye, Michael ;

Alakurtti, Kirsi ;

Kaunisto, Mari A. ;

Haemaelaeinen, Eija ;

de Vries, Boukje ;

Stam, Anine H. ;

Weller, Claudia M. ;

Heinze, Axel ;

Heinze-Kuhn, Katja ;

Goebel, Ingrid ;

Borck, Guntram ;

Goebel, Hartmut ;

Steinberg, Stacy ;

Wolf, Christiane ;

Bjoernsson, Asgeir ;

Gudmundsson, Gretar ;

Kirchmann, Malene ;

Hauge, Anne ;

Werge, Thomas ;

Schoenen, Jean ;

Eriksson, Johan G. ;

Hagen, Knut ;

Stovner, Lars ;

Wichmann, Erich ;

Meitinger, Thomas ;

Alexander, Michael ;

Moebus, Susanne ;

Schreiber, Stefan ;

Aulchenko, Yurii S. ;

Breteler, Monique M. B. ;

Uitterlinden, Andre G. ;

Hofman, Albert ;

van Duijn, Cornelia M. ;

Tikka-Kleemola, Paevi ;

Vepsaelaeinen, Salli ;

Lucae, Susanne ;

Tozzi, Federica ;

Muglia, Pierandrea ;

Barrett, Jeffrey .

NATURE GENETICS, 2010, 42 (10) :869-+

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