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; Anne Francke Christensen; Thomas Folkmann Hansen; Thomas Werge; Jes Olesen; 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, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jes Olesen, International Headache Genetics Consortium

241 Citations (Scopus)

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
Journal	Nature Genetics
Volume	48
Issue number	8
Pages (from-to)	856-66
Number of pages	11
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.3598
Publication status	Published - 1 Aug 2016

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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

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, Christensen, AF, Hansen, TF , Werge, T , Olesen, J & 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

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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.",

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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 - Christensen, Anne Francke

AU - Hansen, Thomas Folkmann

AU - Werge, Thomas

AU - Olesen, Jes

AU - International Headache Genetics Consortium

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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.

KW - Journal Article

U2 - 10.1038/ng.3598

DO - 10.1038/ng.3598

M3 - Journal article

C2 - 27322543

SN - 1061-4036

VL - 48

SP - 856

EP - 866

JO - Nature: New biology

JF - Nature: New biology

IS - 8

ER -

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

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