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

Psychiatric and Neurodevelopmental Genetics Unit
Massachusetts General Hospital
Program in Medical and Population Genetics
Broad Institute
Wellcome Trust Sanger Institute
Analytic and Translational Genetics Unit
University of Oslo
Department of Neurology
Institute of Clinical Medicine
University of Helsinki
University of Tartu
Division of Endocrinology
Boston Children's Hospital
Department of Epidemiology Research
Statens Serum Institut
University of Copenhagen
Illumina, Inc.
Pediatric Neurology
Vall d'Hebron Research Institute
Folkhalsan
Neuroscience Center
Molecular Neurology Research Program
23andMe Inc.
Institute of Public Health
Charité – Universitätsmedizin Berlin
Division of Preventive Medicine
Brigham and Women’s Hospital
Harvard University
deCODE Genetics
University of Bristol
Department of Biological Psychology
Vrije Universiteit Amsterdam
Department of Neurology
Leiden University
Department of Neurology
Helsinki University Hospital
Department of Neurology and Epileptology
University of Tübingen
Ludwig Maximilian University of Munich
Karolinska Institutet
Department of Genetics and Computational Biology
Queensland Institute of Medical Research
Institute of Human Genetics
Ulm University
Center for Life Course Epidemiology and Systems Medicine
University of Oulu
Department of Twin Research and Genetic Epidemiology
King's College London
Department of Epidemiology
Erasmus University Rotterdam
Department of Radiology
Department of Clinical Chemistry
Fimlab Laboratories
Department of Public Health
University of Duisburg-Essen
Landspitali University Hospital
Department of Psychiatry
VU University Medical Center
Department of Psychiatry
Washington University St. Louis
Department of Neurosurgery
University of Eastern Finland

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

556 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

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10.1038/ng.3598

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@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 {\texttimes} 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",

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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

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

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