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

International Headache Genetics Consortium; The International Headache Genetics Consortium

doi:10.1038/ng.3598

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

International Headache Genetics Consortium, The International Headache Genetics Consortium

Research output: Contribution to journal › Article › peer-review

469 Scopus citations

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)	856-866
Number of pages	11
Journal	Nature Genetics
Volume	48
Issue number	8
DOIs	https://doi.org/10.1038/ng.3598
State	Published - Aug 1 2016

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10.1038/ng.3598

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@article{2bf9f3dd10d544f1b7de419494acbe6a,

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 = "{International Headache Genetics Consortium} and {The International Headache Genetics Consortium} and Padhraig Gormley and Verneri Anttila and Winsvold, {Bendik S.} and Priit Palta and Tonu Esko and Pers, {Tune H.} and Farh, {Kai How} 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 Sarin, {Antti Pekka} 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 Hottenga, {Jouke Jan} 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 Reedik M{\"a}gi and Kalle P{\"a}rn and Eija H{\"a}m{\"a}l{\"a}inen and Hailiang Huang and Byrnes, {Andrea E.} and Lude Franke and Jie Huang and Evie Stergiakouli and Lee, {Phil H.} and Cynthia Sandor and Caleb Webber and Zameel Cader and Bertram Muller-Myhsok and Stefan Schreiber and Thomas Meitinger and Eriksson, {Johan G.} and Veikko Salomaa and Kauko Heikkil{\"a} and Elizabeth Loehrer and Uitterlinden, {Andre G.} and Albert Hofman and {van Duijn}, {Cornelia M.} and Lynn Cherkas and Pedersen, {Linda M.} and Audun Stubhaug and Nielsen, {Christopher S.} and Minna M{\"a}nnikk{\"o} and Evelin Mihailov and Lili Milani and Hartmut G{\"o}bel and Esserlind, {Ann Louise} and Christensen, {Anne Francke} and Hansen, {Thomas Folkmann} and Thomas Werge and Jaakko Kaprio and Aromaa, {Arpo J.} and Olli Raitakari and Ikram, {M. Arfan} and Tim Spector and J{\"a}rvelin, {Marjo Riitta} and Andres Metspalu and Christian Kubisch and Strachan, {David P.} and Ferrari, {Michel D.} and Belin, {Andrea Carmine} and Martin Dichgans and Maija Wessman and {van den Maagdenberg}, {Arn M.J.M.} and Zwart, {John Anker} and Boomsma, {Dorret I.} and Smith, {George Davey} and Kari Stefansson and Nicholas Eriksson and Daly, {Mark J.} and Neale, {Benjamin M.} and Jes Olesen and Chasman, {Daniel I.} and Nyholt, {Dale R.} and Aarno Palotie and Sigrid B{\o}rte and Bru Cormand and Else Eising and Michel Ferrari and Frants, {Rune R.} and Lyn Griffiths and Eija Hamalainen and Marjo Hiekkala and Risto Kajanne and Mitja Kurki and Lenore Launer and Davor Lessel and Nadia Litterman and Alfons Macaya and Massimo Mangino and Carrie Northover and Nancy Pedersen and Danielle Posthuma and Patricia Pozo-Rosich and Alice Pressman and Celia Sintas and David Strachan and Marta Vila-Pueyo and William Wrenthal and Huiying Zhao",

year = "2016",

month = aug,

day = "1",

doi = "10.1038/ng.3598",

language = "English",

volume = "48",

pages = "856--866",

journal = "Nature Genetics",

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TY - JOUR

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

AU - International Headache Genetics Consortium

AU - The International Headache Genetics Consortium

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 - Mägi, Reedik

AU - Pärn, Kalle

AU - Hämäläinen, Eija

AU - Huang, Hailiang

AU - Byrnes, Andrea E.

AU - Franke, Lude

AU - Huang, Jie

AU - Stergiakouli, Evie

AU - Lee, Phil H.

AU - Sandor, Cynthia

AU - Webber, Caleb

AU - Cader, Zameel

AU - Muller-Myhsok, Bertram

AU - Schreiber, Stefan

AU - Meitinger, Thomas

AU - Eriksson, Johan G.

AU - Salomaa, Veikko

AU - Heikkilä, Kauko

AU - Loehrer, Elizabeth

AU - Uitterlinden, Andre G.

AU - Hofman, Albert

AU - van Duijn, Cornelia M.

AU - Cherkas, Lynn

AU - Pedersen, Linda M.

AU - Stubhaug, Audun

AU - Nielsen, Christopher S.

AU - Männikkö, Minna

AU - Mihailov, Evelin

AU - Milani, Lili

AU - Göbel, Hartmut

AU - Esserlind, Ann Louise

AU - Christensen, Anne Francke

AU - Hansen, Thomas Folkmann

AU - Werge, Thomas

AU - Kaprio, Jaakko

AU - Aromaa, Arpo J.

AU - Raitakari, Olli

AU - Ikram, M. Arfan

AU - Spector, Tim

AU - Järvelin, Marjo Riitta

AU - Metspalu, Andres

AU - Kubisch, Christian

AU - Strachan, David P.

AU - Ferrari, Michel D.

AU - Belin, Andrea Carmine

AU - Dichgans, Martin

AU - Wessman, Maija

AU - van den Maagdenberg, Arn M.J.M.

AU - Zwart, John Anker

AU - Boomsma, Dorret I.

AU - Smith, George Davey

AU - Stefansson, Kari

AU - Eriksson, Nicholas

AU - Daly, Mark J.

AU - Neale, Benjamin M.

AU - Olesen, Jes

AU - Chasman, Daniel I.

AU - Nyholt, Dale R.

AU - Palotie, Aarno

AU - Børte, Sigrid

AU - Cormand, Bru

AU - Eising, Else

AU - Ferrari, Michel

AU - Frants, Rune R.

AU - Griffiths, Lyn

AU - Hamalainen, Eija

AU - Hiekkala, Marjo

AU - Kajanne, Risto

AU - Kurki, Mitja

AU - Launer, Lenore

AU - Lessel, Davor

AU - Litterman, Nadia

AU - Macaya, Alfons

AU - Mangino, Massimo

AU - Northover, Carrie

AU - Pedersen, Nancy

AU - Posthuma, Danielle

AU - Pozo-Rosich, Patricia

AU - Pressman, Alice

AU - Sintas, Celia

AU - Strachan, David

AU - Vila-Pueyo, Marta

AU - Wrenthal, William

AU - Zhao, Huiying

PY - 2016/8/1

Y1 - 2016/8/1

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.

UR - http://www.scopus.com/inward/record.url?scp=84975318713&partnerID=8YFLogxK

U2 - 10.1038/ng.3598

DO - 10.1038/ng.3598

M3 - Article

C2 - 27322543

AN - SCOPUS:84975318713

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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