Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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27322543
TITLE
Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.
ABSTRACT
NlmCategory: UNASSIGNED
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.
DATE PUBLISHED
2016 Jun 20
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2015/10/27
accepted 2016/05/26
entrez 2016/06/21 06:00
pubmed 2016/06/21 06:00
medline 2016/06/21 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Gormley P Gormley Padhraig P Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
Anttila V Anttila Verneri V Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Winsvold BS Winsvold Bendik S BS Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Palta P Palta Priit P Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Esko T Esko Tonu T Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.
Pers TH Pers Tune H TH Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Farh KH Farh Kai-How KH Illumina, San Diego, California, USA.
Cuenca-Leon E Cuenca-Leon Ester E Pediatric Neurology, Vall d'Hebron Research Institute, Barcelona, Spain.
Muona M Muona Mikko M Molecular Neurology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
Furlotte NA Furlotte Nicholas A NA 23andMe, Inc., Mountain View, California, USA.
Kurth T Kurth Tobias T Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Ingason A Ingason Andres A deCODE Genetics, Reykjavik, Iceland.
McMahon G McMahon George G Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Ligthart L Ligthart Lannie L Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
Terwindt GM Terwindt Gisela M GM Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
Kallela M Kallela Mikko M Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
Freilinger TM Freilinger Tobias M TM Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.
Ran C Ran Caroline C Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Gordon SG Gordon Scott G SG Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Stam AH Stam Anine H AH Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
Steinberg S Steinberg Stacy S deCODE Genetics, Reykjavik, Iceland.
Borck G Borck Guntram G Institute of Human Genetics, Ulm University, Ulm, Germany.
Koiranen M Koiranen Markku M Center for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland.
Quaye L Quaye Lydia L Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Adams HH Adams Hieab H H HH Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Lehtimäki T Lehtimäki Terho T Department of Clinical Chemistry, Fimlab Laboratories, School of Medicine, University of Tampere, Tampere, Finland.
Sarin AP Sarin Antti-Pekka AP Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Wedenoja J Wedenoja Juho J Department of Public Health, University of Helsinki, Helsinki, Finland.
Hinds DA Hinds David A DA 23andMe, Inc., Mountain View, California, USA.
Buring JE Buring Julie E JE Harvard Medical School, Boston, Massachusetts, USA.
Schürks M Schürks Markus M Department of Neurology, University Duisburg-Essen, Essen, Germany.
Ridker PM Ridker Paul M PM Harvard Medical School, Boston, Massachusetts, USA.
Hrafnsdottir MG Hrafnsdottir Maria Gudlaug MG Landspitali University Hospital, Reykjavik, Iceland.
Stefansson H Stefansson Hreinn H deCODE Genetics, Reykjavik, Iceland.
Ring SM Ring Susan M SM Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Hottenga JJ Hottenga Jouke-Jan JJ Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
Penninx BW Penninx Brenda W J H BW Department of Psychiatry, VU University Medical Centre, Amsterdam, the Netherlands.
Färkkilä M Färkkilä Markus M Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
Artto V Artto Ville V Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
Kaunisto M Kaunisto Mari M Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Vepsäläinen S Vepsäläinen Salli S Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
Malik R Malik Rainer R Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Madden PA Madden Pamela A F PA Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Martin NG Martin Nicholas G NG Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Montgomery GW Montgomery Grant W GW Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Kurki MI Kurki Mitja I MI Department of Neurosurgery, NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
Kals M Kals Mart M Estonian Genome Center, University of Tartu, Tartu, Estonia.
Mägi R Mägi Reedik R Estonian Genome Center, University of Tartu, Tartu, Estonia.
Pärn K Pärn Kalle K Estonian Genome Center, University of Tartu, Tartu, Estonia.
Hämäläinen E Hämäläinen Eija E Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Huang H Huang Hailiang H Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Byrnes AE Byrnes Andrea E AE Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Franke L Franke Lude L Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Huang J Huang Jie J Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
Stergiakouli E Stergiakouli Evie E Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Lee PH Lee Phil H PH Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Sandor C Sandor Cynthia C MRC Functional Genomics Unit, Department of Physiology, Anatomy &Genetics, Oxford University, Oxford, UK.
Webber C Webber Caleb C MRC Functional Genomics Unit, Department of Physiology, Anatomy &Genetics, Oxford University, Oxford, UK.
Cader Z Cader Zameel Z Oxford Headache Centre, John Radcliffe Hospital, Oxford, UK.
Muller-Myhsok B Muller-Myhsok Bertram B Max Planck Institute of Psychiatry, Munich, Germany.
Schreiber S Schreiber Stefan S Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany.
Meitinger T Meitinger Thomas T Institute of Human Genetics, Technische Universität München, Munich, Germany.
Eriksson JG Eriksson Johan G JG National Institute for Health and Welfare, Helsinki, Finland.
Salomaa V Salomaa Veikko V National Institute for Health and Welfare, Helsinki, Finland.
Heikkilä K Heikkilä Kauko K Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland.
Loehrer E Loehrer Elizabeth E Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Uitterlinden AG Uitterlinden Andre G AG Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Hofman A Hofman Albert A Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
van Duijn CM van Duijn Cornelia M CM Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Cherkas L Cherkas Lynn L Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Pedersen LM Pedersen Linda M LM FORMI, Oslo University Hospital, Oslo, Norway.
Stubhaug A Stubhaug Audun A Medical Faculty, University of Oslo, Oslo, Norway.
Nielsen CS Nielsen Christopher S CS Department of Ageing and Health, Norwegian Institute of Public Health, Oslo, Norway.
Männikkö M Männikkö Minna M Center for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland.
Mihailov E Mihailov Evelin E Estonian Genome Center, University of Tartu, Tartu, Estonia.
Milani L Milani Lili L Estonian Genome Center, University of Tartu, Tartu, Estonia.
Göbel H Göbel Hartmut H Kiel Pain and Headache Center, Kiel, Germany.
Esserlind AL Esserlind Ann-Louise AL Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.
Christensen AF Christensen Anne Francke AF Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.
Hansen TF Hansen Thomas Folkmann TF Institute of Biological Psychiatry, Mental Health Center Sct. Hans, University of Copenhagen, Roskilde, Denmark.
Werge T Werge Thomas T iPSYCH-The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
International Headache Genetics Consortium
Kaprio J Kaprio Jaakko J Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
Aromaa AJ Aromaa Arpo J AJ National Institute for Health and Welfare, Helsinki, Finland.
Raitakari O Raitakari Olli O Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
Ikram MA Ikram M Arfan MA Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Spector T Spector Tim T Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Järvelin MR Järvelin Marjo-Riitta MR Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu, Tartu, Estonia.
Kubisch C Kubisch Christian C Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Strachan DP Strachan David P DP Population Health Research Institute, St George's, University of London, London, UK.
Ferrari MD Ferrari Michel D MD Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
Belin AC Belin Andrea C AC Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Dichgans M Dichgans Martin M Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Wessman M Wessman Maija M Folkhälsan Institute of Genetics, Helsinki, Finland.
van den Maagdenberg AM van den Maagdenberg Arn M J M AM Department of Human Genetics, Leiden University Medical Centre, Leiden, the Netherlands.
Zwart JA Zwart John-Anker JA Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
Smith GD Smith George Davey GD Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Stefansson K Stefansson Kari K Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Eriksson N Eriksson Nicholas N 23andMe, Inc., Mountain View, California, USA.
Daly MJ Daly Mark J MJ Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Neale BM Neale Benjamin M BM Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Olesen J Olesen Jes J Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.
Chasman DI Chasman Daniel I DI Harvard Medical School, Boston, Massachusetts, USA.
Nyholt DR Nyholt Dale R DR Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
Palotie A Palotie Aarno A Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Anttila Verneri V
Artto Ville V
Belin Andrea Carmine AC
Boomsma Dorret I DI
Børte Sigrid S
Chasman Daniel I DI
Cherkas Lynn L
Christensen Anne Francke AF
Cormand Bru B
Cuenca-Leon Ester E
Smith George Davey GD
Dichgans Martin M
van Duijn Cornelia C
Eising Else E
Esko Tonu T
Esserlind Ann-Louise AL
Ferrari Michel M
Frants Rune R RR
Freilinger Tobias M TM
Furlotte Nicholas A NA
Gormley Padhraig P
Griffiths Lyn L
Hamalainen Eija E
Hansen Thomas Folkmann TF
Hiekkala Marjo M
Ikram M Arfan MA
Ingason Andres A
Järvelin Marjo-Riitta MR
Kajanne Risto R
Kallela Mikko M
Kaprio Jaakko J
Kaunisto Mari M
Kubisch Christian C
Kurki Mitja M
Kurth Tobias T
Launer Lenore L
Lehtimaki Terho T
Lessel Davor D
Ligthart Lannie L
Litterman Nadia N
van den Maagdenberg Arn M J M AM
Macaya Alfons A
Malik Rainer R
Mangino Massimo M
McMahon George G
Muller-Myhsok Bertram B
Neale Benjamin M BM
Northover Carrie C
Nyholt Dale R DR
Olesen Jes J
Palotie Aarno A
Palta Priit P
Pedersen Linda M LM
Pedersen Nancy N
Posthuma Danielle D
Pozo-Rosich Patricia P
Pressman Alice A
Quaye Lydia L
Raitakari Olli O
Schürks Markus M
Sintas Celia C
Stefansson Kari K
Stefansson Hreinn H
Steinberg Stacy S
Strachan David D
Terwindt Gisela M GM
Vila-Pueyo Marta M
Wessman Maija M
Winsvold Bendik S BS
Wrenthal William W
Zhao Huiying H
Zwart John-Anker JA
JOURNAL
VOLUME:
ISSUE:
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2016
MONTH: Jun
DAY: 20
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
JOURNAL ARTICLE
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