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

Padhraig Gormley; Verneri Anttila; Bendik S Winsvold; Priit Palta; Tonu Esko; Tune H Pers; Kai-How Farh; Ester Cuenca-Leon; Mikko Muona; Nicholas A Furlotte; Tobias Kurth; Andres Ingason; George McMahon; Lannie Ligthart; Gisela M Terwindt; Mikko Kallela; Tobias M Freilinger; Caroline Ran; Scott G Gordon; Anine H Stam; Stacy Steinberg; Guntram Borck; Markku Koiranen; Lydia Quaye; Hieab H H Adams; Terho Lehtimäki; Antti-Pekka Sarin; Juho Wedenoja; David A Hinds; Julie E Buring; Markus Schürks; Paul M Ridker; Maria Gudlaug Hrafnsdottir; Hreinn Stefansson; Susan M Ring; Jouke-Jan Hottenga; Brenda W J H Penninx; Markus Färkkilä; Ville Artto; Mari Kaunisto; Salli Vepsäläinen; Rainer Malik; Andrew C Heath; Pamela A F Madden; Nicholas G Martin; Grant W Montgomery; Mitja I Kurki; Mart Kals; Evie Stergiakouli; George Davey Smith; International Headache Genetics Consortium

doi:10.1038/ng.3598

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

Padhraig Gormley, Verneri Anttila, Bendik S Winsvold, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H StamStacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Evie Stergiakouli, George Davey Smith, International Headache Genetics Consortium

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Abstract

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 × 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.

Original language	English
Pages (from-to)	856-66
Number of pages	11
Journal	Nature Genetics
Volume	48
Issue number	8
Early online date	20 Jun 2016
DOIs	https://doi.org/10.1038/ng.3598
Publication status	Published - Aug 2016

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Timpson, N. J. (Principal Investigator) & Timpson, N. J. (Principal Investigator)
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MRC UoB UNITE Unit - Programme 1
Davey Smith, G. (Principal Investigator)
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CENTRE FOR CASUAL ANALYSES IN TRANSLATIONAL EPIDEMIOLOGY (CAiTE)
Davey Smith, G. (Principal Investigator)
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Professor George Davey Smith
- KZ.Davey-Smithbristol.acuk
- MRC Integrative Epidemiology Unit
- Bristol Medical School (PHS) - Professor of Clinical Epidemiology
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Professor Evangelia Stergiakouli
- E.Stergiakoulibristol.acuk
- Bristol Medical School (PHS) - Professor of Genetic Epidemiology and Public Mental Health
- Bristol Population Health Science Institute
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Gormley, P., Anttila, V., Winsvold, B. S., Palta, P., Esko, T., Pers, T. H., Farh, K.-H., Cuenca-Leon, E., Muona, M., Furlotte, N. A., Kurth, T., Ingason, A., McMahon, G., Ligthart, L., Terwindt, G. M., Kallela, M., Freilinger, T. M., Ran, C., Gordon, S. G., ... International Headache Genetics Consortium (2016). Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nature Genetics, 48(8), 856-66. https://doi.org/10.1038/ng.3598

@article{b7c1662806b240d990dc4904870bc80d,

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

abstract = "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 × 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.",

author = "Padhraig Gormley and Verneri Anttila and Winsvold, {Bendik S} and Priit Palta and Tonu Esko and Pers, {Tune H} and Kai-How Farh and Ester Cuenca-Leon and Mikko Muona and Furlotte, {Nicholas A} and Tobias Kurth and Andres Ingason and George McMahon and Lannie Ligthart and Terwindt, {Gisela M} and Mikko Kallela and Freilinger, {Tobias M} and Caroline Ran and Gordon, {Scott G} and Stam, {Anine H} and Stacy Steinberg and Guntram Borck and Markku Koiranen and Lydia Quaye and Adams, {Hieab H H} and Terho Lehtim{\"a}ki and Antti-Pekka Sarin and Juho Wedenoja and Hinds, {David A} and Buring, {Julie E} and Markus Sch{\"u}rks and Ridker, {Paul M} and Hrafnsdottir, {Maria Gudlaug} and Hreinn Stefansson and Ring, {Susan M} and Jouke-Jan Hottenga and Penninx, {Brenda W J H} and Markus F{\"a}rkkil{\"a} and Ville Artto and Mari Kaunisto and Salli Veps{\"a}l{\"a}inen and Rainer Malik and Heath, {Andrew C} and Madden, {Pamela A F} and Martin, {Nicholas G} and Montgomery, {Grant W} and Kurki, {Mitja I} and Mart Kals and Evie Stergiakouli and Smith, {George Davey} and {International Headache Genetics Consortium}",

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month = aug,

doi = "10.1038/ng.3598",

language = "English",

volume = "48",

pages = "856--66",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Springer Nature",

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}

Gormley, P, Anttila, V, Winsvold, BS, Palta, P, Esko, T, Pers, TH, Farh, K-H, Cuenca-Leon, E, Muona, M, Furlotte, NA, Kurth, T, Ingason, A, McMahon, G, Ligthart, L, Terwindt, GM, Kallela, M, Freilinger, TM, Ran, C, Gordon, SG, Stam, AH, Steinberg, S, Borck, G, Koiranen, M, Quaye, L, Adams, HHH, Lehtimäki, T, Sarin, A-P, Wedenoja, J, Hinds, DA, Buring, JE, Schürks, M, Ridker, PM, Hrafnsdottir, MG, Stefansson, H, Ring, SM, Hottenga, J-J, Penninx, BWJH, Färkkilä, M, Artto, V, Kaunisto, M, Vepsäläinen, S, Malik, R, Heath, AC, Madden, PAF, Martin, NG, Montgomery, GW, Kurki, MI, Kals, M, Stergiakouli, E , Smith, GD & International Headache Genetics Consortium 2016, 'Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine', Nature Genetics, vol. 48, no. 8, pp. 856-66. https://doi.org/10.1038/ng.3598

TY - JOUR

T1 - Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

AU - Gormley, Padhraig

AU - Anttila, Verneri

AU - Winsvold, Bendik S

AU - Palta, Priit

AU - Esko, Tonu

AU - Pers, Tune H

AU - Farh, Kai-How

AU - Cuenca-Leon, Ester

AU - Muona, Mikko

AU - Furlotte, Nicholas A

AU - Kurth, Tobias

AU - Ingason, Andres

AU - McMahon, George

AU - Ligthart, Lannie

AU - Terwindt, Gisela M

AU - Kallela, Mikko

AU - Freilinger, Tobias M

AU - Ran, Caroline

AU - Gordon, Scott G

AU - Stam, Anine H

AU - Steinberg, Stacy

AU - Borck, Guntram

AU - Koiranen, Markku

AU - Quaye, Lydia

AU - Adams, Hieab H H

AU - Lehtimäki, Terho

AU - Sarin, Antti-Pekka

AU - Wedenoja, Juho

AU - Hinds, David A

AU - Buring, Julie E

AU - Schürks, Markus

AU - Ridker, Paul M

AU - Hrafnsdottir, Maria Gudlaug

AU - Stefansson, Hreinn

AU - Ring, Susan M

AU - Hottenga, Jouke-Jan

AU - Penninx, Brenda W J H

AU - Färkkilä, Markus

AU - Artto, Ville

AU - Kaunisto, Mari

AU - Vepsäläinen, Salli

AU - Malik, Rainer

AU - Heath, Andrew C

AU - Madden, Pamela A F

AU - Martin, Nicholas G

AU - Montgomery, Grant W

AU - Kurki, Mitja I

AU - Kals, Mart

AU - Stergiakouli, Evie

AU - Smith, George Davey

AU - International Headache Genetics Consortium

PY - 2016/8

Y1 - 2016/8

N2 - 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 × 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.

AB - 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 × 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.

U2 - 10.1038/ng.3598

DO - 10.1038/ng.3598

M3 - Article (Academic Journal)

C2 - 27322543

SN - 1061-4036

VL - 48

SP - 856

EP - 866

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

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

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MRC UoB UNITE Unit - Programme 1

CENTRE FOR CASUAL ANALYSES IN TRANSLATIONAL EPIDEMIOLOGY (CAiTE)

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Cite this