Evidence map›Paper›PMID 27322543›Full record

SynthesisNature genetics2016

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 and 98 more

Erratum issuedOpen access · greenAbstract readComparative StudyMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Nature genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 352 papers, 21 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
352citing papers in PubMed, 21 pooled it
50.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

352 citing papers in PubMed, 21 syntheses or guidelines pooled it, 693 citations in OpenAlex.

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  5. What does a migraine aura look like?-A systematic review.The journal of headache and pain · 2025
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292 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

108 authors at 20 institutions in 12 countries.

Padhraig GormleyPsychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Verneri AnttilaMedical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.ORCID 0000-0002-0073-4675
Bendik S WinsvoldFORMI, Oslo University Hospital, Oslo, Norway.
Priit PaltaInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Tonu EskoMedical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.ORCID 0000-0003-1982-6569
Tune H PersMedical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Kai-How FarhMedical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Ester Cuenca-LeonPsychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Mikko MuonaInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.ORCID 0000-0002-0949-6650
Nicholas A Furlotte23andMe, Inc., Mountain View, California, USA.
Tobias KurthInstitute of Public Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Andres IngasondeCODE Genetics, Reykjavik, Iceland.
George McMahonMedical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Lannie LigthartDepartment of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
Gisela M TerwindtDepartment of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
Mikko KallelaDepartment of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
Tobias M FreilingerDepartment of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
Caroline RanDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-0239-9871
Scott G GordonDepartment of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Anine H StamDepartment of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
Stacy SteinbergdeCODE Genetics, Reykjavik, Iceland.
Guntram BorckInstitute of Human Genetics, Ulm University, Ulm, Germany.ORCID 0000-0003-2279-8052
Markku KoiranenCenter for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland.
Lydia QuayeDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Hieab H H AdamsDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID 0000-0003-3687-2508
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, School of Medicine, University of Tampere, Tampere, Finland.
Antti-Pekka SarinInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Juho WedenojaDepartment of Public Health, University of Helsinki, Helsinki, Finland.
David A Hinds23andMe, Inc., Mountain View, California, USA.
Julie E BuringDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Markus SchürksDepartment of Neurology, University Duisburg-Essen, Essen, Germany.
Paul M RidkerDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Maria Gudlaug HrafnsdottirLandspitali University Hospital, Reykjavik, Iceland.
Hreinn StefanssondeCODE Genetics, Reykjavik, Iceland.
Susan M RingMedical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Jouke-Jan HottengaDepartment of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
Brenda W J H PenninxDepartment of Psychiatry, VU University Medical Centre, Amsterdam, the Netherlands.
Markus FärkkiläDepartment of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
Ville ArttoDepartment of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
Mari KaunistoInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Salli VepsäläinenDepartment of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
Rainer MalikInstitute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.
Andrew C HeathDepartment of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Pamela A F MaddenDepartment of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Nicholas G MartinDepartment of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Grant W MontgomeryDepartment of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Mitja I KurkiPsychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Mart KalsEstonian Genome Center, University of Tartu, Tartu, Estonia.
Reedik MägiEstonian Genome Center, University of Tartu, Tartu, Estonia.
Kalle PärnEstonian Genome Center, University of Tartu, Tartu, Estonia.
Eija HämäläinenInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Hailiang HuangMedical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.ORCID 0000-0003-1461-5762
Andrea E ByrnesMedical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Lude FrankeDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.ORCID 0000-0002-5159-8802
Jie HuangWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
Evie StergiakouliMedical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Phil H LeePsychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Cynthia SandorMRC Functional Genomics Unit, Department of Physiology, Anatomy &Genetics, Oxford University, Oxford, UK.
Caleb WebberMRC Functional Genomics Unit, Department of Physiology, Anatomy &Genetics, Oxford University, Oxford, UK.
Zameel CaderNuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.
Bertram Muller-MyhsokMax Planck Institute of Psychiatry, Munich, Germany.
Stefan SchreiberInstitute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany.
Thomas MeitingerInstitute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
Johan G ErikssonDepartment of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Veikko SalomaaNational Institute for Health and Welfare, Helsinki, Finland.
Kauko HeikkiläInstitute of Clinical Medicine, University of Helsinki, Helsinki, Finland.
Elizabeth LoehrerDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Andre G UitterlindenDepartment of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Albert HofmanDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Cornelia M van DuijnDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Lynn CherkasDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Linda M PedersenFORMI, Oslo University Hospital, Oslo, Norway.
Audun StubhaugDepartment of Pain Management and Research, Oslo University Hospital, Oslo, Norway.
Christopher S NielsenDepartment of Pain Management and Research, Oslo University Hospital, Oslo, Norway.ORCID 0000-0003-0678-331X
Minna MännikköCenter for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland.
Evelin MihailovEstonian Genome Center, University of Tartu, Tartu, Estonia.
Lili MilaniEstonian Genome Center, University of Tartu, Tartu, Estonia.ORCID 0000-0002-5323-3102
Hartmut GöbelKiel Pain and Headache Center, Kiel, Germany.
Ann-Louise EsserlindDanish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.
Anne Francke ChristensenDanish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.
Thomas Folkmann HansenInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, University of Copenhagen, Roskilde, Denmark.ORCID 0000-0001-6703-7762
Thomas WergeInstitute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Copenhagen, Denmark.
International Headache Genetics Consortium
Jaakko KaprioInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.ORCID 0000-0002-3716-2455
Arpo J AromaaNational Institute for Health and Welfare, Helsinki, Finland.
Olli RaitakariResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
M Arfan IkramDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID 0000-0003-0372-8585
Tim SpectorDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Marjo-Riitta JärvelinCenter for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland.
Andres MetspaluEstonian Genome Center, University of Tartu, Tartu, Estonia.
Christian KubischInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
David P StrachanPopulation Health Research Institute, St George's, University of London, London, UK.ORCID 0000-0001-7854-1366
Michel D FerrariDepartment of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
Andrea C BelinDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Martin DichgansInstitute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.
Maija WessmanInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Arn M J M van den MaagdenbergDepartment of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
John-Anker ZwartFORMI, Oslo University Hospital, Oslo, Norway.
Dorret I BoomsmaDepartment of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
George Davey SmithMedical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Kari StefanssondeCODE Genetics, Reykjavik, Iceland.
Nicholas Eriksson23andMe, Inc., Mountain View, California, USA.
Mark J DalyMedical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.ORCID 0000-0002-0949-8752
Benjamin M NealeMedical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.ORCID 0000-0003-1513-6077
Jes OlesenDanish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.
Daniel I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Dale R NyholtStatistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
Aarno PalotiePsychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Broad Institute · USUniversity of Helsinki · FIUniversity of Tartu · EEErasmus MC · NLOslo University Hospital · NOUniversity of Copenhagen · DKBrigham and Women's Hospital · USdeCODE Genetics (Iceland) · ISHelsinki University Hospital · FIUniversity of Bristol · GB23andMe (United States) · USKing's College London · GBLeiden University Medical Center · NLQIMR Berghofer Medical Research Institute · AUVrije Universiteit Amsterdam · NLFinnish Institute for Health and Welfare · FIHarvard University · USKarolinska Institutet · SEUniversity of Oulu · FIUniversity of Oxford · GB

Funding

NIMH Center Repository Supporting Stem Cell ResearchU24MH068457 · NIMH · RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK · PI BRZUSTOWICZ, LINDA M, KNOWLES, JAMES A · 2003 to 2024
$213.8M
Type 1 Diabetes Genetics ConsortiumU01DK062418 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI RICH, STEPHEN S. · 2002 to 2007
$59.8M
Women's Health Study: Continued Follow-upR01CA047988 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 1991 to 2014
$28.2M
PILOT--GENETIC EPIDEMIOLOGY OF ALCOHOL AND TOBACCO CONSUMPTION IN CHINESE SAMPLEP50AA011998 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 1999 to 2008
$12.6M
TRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0M
THE GENETICS OF VULNERABILITY TO NICOTINE ADDICTIONSR01DA012854 · NIDA · WASHINGTON UNIVERSITY · PI MADDEN, PAMELA ANN · 2000 to 2013
$10.4M
Integration of Genomics & Transcriptomics in Normal Twins & Major DepressionRC2MH089951 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SULLIVAN, PATRICK F · 2009 to 2010
$6.5M
Women's Health Study: Continued Follow-UpR01HL080467 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E. · 2005 to 2010
$4.5M
Molecular Epidemiology of Alcoholism 3 - EDAC FamiliesR01AA013321 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 2001 to 2005
$4.3M
RESEARCH EDUCATION PROGRAM ON COMPUTATIONAL AND STATISTICAL TOOL DEVELOPMENT FOR ADDICTION GENETICSR25DA027995 · NIDA · WASHINGTON UNIVERSITY · PI MADDEN, PAMELA ANN, RICE, JOHN P. · 2009 to 2019
$4.3M
The Women's Health Study: Infrastructure Support for Continued Cohort Follow-upUM1CA182913 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 2014 to 2018
$4.0M
Genetics of cardiovascular risk factors in large founder population birth controlR01HL087679 · NHLBI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HIRSCHHORN, JOEL N · 2007 to 2009
$4.0M
Medical Research Council G0000934Medical Research Council G0500539Medical Research Council G0600705Medical Research Council G1002319Medical Research Council MC_PC_15018Medical Research Council MC_UP_A320_1004Medical Research Council MC_UU_00002/10Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/3Medical Research Council MC_UU_12021/4NCI NIH HHS R01 CA047988NCI NIH HHS UM1 CA182913NHGRI NIH HHS R44 HG006981NHLBI NIH HHS R01 HL043851NHLBI NIH HHS R01 HL080467NHLBI NIH HHS R01 HL087679NIAAA NIH HHS K05 AA017688NIAAA NIH HHS P50 AA011998NIAAA NIH HHS R01 AA007535NIAAA NIH HHS R01 AA007728NIAAA NIH HHS R01 AA010249NIAAA NIH HHS R01 AA013320NIAAA NIH HHS R01 AA013321NIAAA NIH HHS R01 AA014041NICHD NIH HHS R01 HD042157NIDA NIH HHS K08 DA019951NIDA NIH HHS R01 DA012854NIDA NIH HHS R25 DA027995NIDA NIH HHS R37 DA018673NIDCR NIH HHS R01 DE022905NIDDK NIH HHS U01 DK062418NIGMS NIH HHS T32 GM007748NIMH NIH HHS K99 MH101367NIMH NIH HHS R01 MH063706NIMH NIH HHS R01 MH081802NIMH NIH HHS RC2 MH089951NIMH NIH HHS RC2 MH089995NIMH NIH HHS RL1 MH083268NIMH NIH HHS U24 MH068457NINDS NIH HHS R21 NS092963Wellcome Trust 068545/Z/02Wellcome Trust 076113/B/04/ZWellcome Trust 079895Wellcome Trust 098051Wellcome Trust 102215Wellcome Trust WT089062
6 · The paper itself

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.

Indexed as

Genetic Predisposition to DiseaseCase-Control StudiesGenetic LociGenetic MarkersGenome-Wide Association StudyGenomicsHumansMigraine DisordersMuscle, SmoothPolymorphism, Single NucleotideVascular DiseasesGenetic Markers

Identifiers

PMID27322543
PMCPMC5331903
OpenAlexW2464448281

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.