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

Massachusetts General Hospital
Broad Institute
Wellcome Trust Sanger Institute
University of Oslo
University of Helsinki
University of Tartu
Boston Children's Hospital
Statens Serum Institut
University of Copenhagen
Illumina, Inc.
Vall d'Hebron Research Institute
Folkhalsan
23andMe Inc.
Charité – Universitätsmedizin Berlin
Brigham and Women’s Hospital
Harvard University
deCODE Genetics
University of Bristol
Vrije Universiteit Amsterdam
Leiden University
Helsinki University Hospital
University of Tübingen
Ludwig Maximilian University of Munich
Karolinska Institutet
Queensland Institute of Medical Research
Ulm University
University of Oulu
King's College London
Erasmus University Rotterdam
Fimlab Laboratories
University of Duisburg-Essen
Landspitali University Hospital
VU University Medical Center
Washington University St. Louis
University of Eastern Finland
University of Groningen
University of Oxford
John Radcliffe Hospital
Max Planck Institute of Psychiatry
Munich Cluster for Systems Neurology (SyNergy)
University of Liverpool
Kiel University
Helmholtz Zentrum München - German Research Center for Environmental Health
Technical University of Munich
National Institute for Health and Welfare
Norwegian Institute of Public Health
Kiel Pain and Headache Center
MHC Sct. Hans
H. Lundbeck A/S
University of Turku
Imperial College London
University of Hamburg
St. George's University of London
University of Iceland
Queensland University of Technology
University of Barcelona
National Institutes of Health
Autonomous University of Barcelona
University Hospital Vall d'Hebron
Sutter Health

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

528 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
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
Publication status	Published - 1 Aug 2016
Externally published	Yes

Access to Document

10.1038/ng.3598

Cite this

@article{1281ffddd0bc4ee09c7d8c62c67f1ebd,

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",

year = "2016",

month = aug,

day = "1",

doi = "10.1038/ng.3598",

language = "English",

volume = "48",

pages = "856--866",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "8",

}

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

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 - https://www.scopus.com/pages/publications/84975318713

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this