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

Title: Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.
Authors: Gormley, Padhraig; Anttila, Verneri; Winsvold, Bendik S; Palta, Priit; Esko, Tonu; Pers, Tune H; Farh, Kai-How; Cuenca-Leon, Ester; Muona, Mikko; Furlotte, Nicholas A; Kurth, Tobias; Dichgans, Martin; Wessman, Maija; van den Maagdenberg, Arn M J M; Zwart, John-Anker; Boomsma, Dorret I; Smith, George Davey; Stefansson, Kari; Eriksson, Nicholas; Daly, Mark J; Neale, Benjamin M; Olesen, Jes; Chasman, Daniel I; Nyholt, Dale R; Palotie, Aarno; Ingason, Andres; McMahon, George; Ligthart, Lannie; Terwindt, Gisela M; Kallela, Mikko; Freilinger, Tobias M; Ran, Caroline; Gordon, Scott G; Stam, Anine H; Steinberg, Stacy; Borck, Guntram; Koiranen, Markku; Quaye, Lydia; Adams, Hieab H H; Lehtimäki, Terho; Sarin, Antti-Pekka; Wedenoja, Juho; Hinds, David A; Buring, Julie E; Schürks, Markus; Ridker, Paul M; Hrafnsdottir, Maria Gudlaug; Stefansson, Hreinn; Ring, Susan M; Hottenga, Jouke-Jan; Penninx, Brenda W J H; Färkkilä, Markus; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Malik, Rainer; Heath, Andrew C; Madden, Pamela A F; Martin, Nicholas G; Montgomery, Grant W; Kurki, Mitja I; Kals, Mart; Mägi, Reedik; Pärn, Kalle; Hämäläinen, Eija; Huang, Hailiang; Byrnes, Andrea E; Franke, Lude; Huang, Jie; Stergiakouli, Evie; Lee, Phil H; Sandor, Cynthia; Webber, Caleb; Cader, Zameel; Muller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Eriksson, Johan G; Salomaa, Veikko; Heikkilä, Kauko; Loehrer, Elizabeth; Uitterlinden, Andre G; Hofman, Albert; van Duijn, Cornelia M; Cherkas, Lynn; Pedersen, Linda M; Stubhaug, Audun; Nielsen, Christopher S; Männikkö, Minna; Mihailov, Evelin; Milani, Lili; Göbel, Hartmut; Esserlind, Ann-Louise; Christensen, Anne Francke; Hansen, Thomas Folkmann; Werge, Thomas; Kaprio, Jaakko; Aromaa, Arpo J; Raitakari, Olli; Ikram, M Arfan; Spector, Tim; Järvelin, Marjo-Riitta; Metspalu, Andres; Kubisch, Christian; Strachan, David P; Ferrari, Michel D; Belin, Andrea C
Contributors: a Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States b Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, United States c Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, United States d Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom e Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States f FORMI, Oslo University Hospital, Oslo, Norway g Department of Neurology, Oslo University Hospital, Oslo, Norway h Institute of Clinical Medicine, University of Oslo, Oslo, Norway i Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland j Estonian Genome Center, University of Tartu, Tartu, Estonia k Division of Endocrinology, Boston Children's Hospital, Boston, MA, United States l Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark m Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark n Illumina, San Diego, CA, United States o Pediatric Neurology, Vall D'Hebron Research Institute, Barcelona, Spain p Folkhälsan Institute of Genetics, Helsinki, Finland q Neuroscience Center, University of Helsinki, Helsinki, Finland r Molecular Neurology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland s 23andMe, Inc., Mountain View, CA, United States t Institute of Public Health, Charité-Universitätsmedizin Berlin, Berlin, Germany u Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, United States v DeCODE Genetics, Reykjavik, Iceland w Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom x Department of Biological Psychology, Vrije Universiteit, Amsterdam, Netherlands y Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands z Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland aa Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany ab Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany ac Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden ad Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia ae Institute of Human Genetics, Ulm University, Ulm, Germany af Center for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland ag Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom ah Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands ai Department of Radiology, Erasmus University Medical Center, Rotterdam, Netherlands aj Department of Clinical Chemistry, Fimlab Laboratories, School of Medicine, University of Tampere, Tampere, Finland ak Department of Public Health, University of Helsinki, Helsinki, Finland al Harvard Medical School, Boston, MA, United States am Department of Neurology, University Duisburg-Essen, Essen, Germany an Landspitali University Hospital, Reykjavik, Iceland ao Department of Psychiatry, VU University Medical Centre, Amsterdam, Netherlands ap Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States aq Department of Neurosurgery, NeuroCenter, Kuopio University Hospital, Kuopio, Finland ar Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands as MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, Oxford University, Oxford, United Kingdom at Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom au Oxford Headache Centre, John Radcliffe Hospital, Oxford, United Kingdom av Max Planck Institute of Psychiatry, Munich, Germany aw Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany ax Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany ay Institute of Human Genetics, Technische Universität München, Munich, Germany az Department of General Practice and Primary Health Care, University of Helsinki, Helsinki University Hospital, Helsinki, Finland ba National Institute for Health and Welfare, Helsinki, Finland bb Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland bc Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States bd Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands be Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway bf Medical Faculty, University of Oslo, Oslo, Norway bg Department of Ageing and Health, Norwegian Institute of Public Health, Oslo, Norway bh Kiel Pain and Headache Center, Kiel, Germany bi Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark bj Institute of Biological Psychiatry, Mental Health Center Sct. Hans, University of Copenhagen, Roskilde, Denmark bk Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Copenhagen, Denmark bl Institute of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Copenhagen, Copenhagen, Denmark bm IPSYCH-The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark bn Department of Health, National Institute for Health and Welfare, Helsinki, Finland bo Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland bp Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland bq Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands br Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE), Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom bs Biocenter Oulu, University of Oulu, Oulu, Finland bt Unit of Primary Care, Oulu University Hospital, Oulu, Finland bu Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany bv Population Health Research Institute, St George's, University of London, London, United Kingdom bw Munich Cluster for Systems Neurology (SyNergy), Munich, Germany bx Department of Human Genetics, Leiden University Medical Centre, Leiden, Netherlands by Faculty of Medicine, University of Iceland, Reykjavik, Iceland bz Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia ca Department of Neurology, Massachusetts General Hospital, Boston, MA, United States cb Department of Neurology, Oslo University Hospital, University of Oslo, Oslo, Norway cc Department of Genetics, University of Barcelona, Barcelona, Spain cd Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia ce National Institute on Aging, Bethesda, MD, United States cf Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden cg Department of Clinical Genetics, Vrije Universiteit, Amsterdam, Netherlands ch Headache Research Group, Vall D'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain ci Sutter Health, Sacramento, CA, United States cj Department of Medicine, University of Turku, Turku, Finland ck Broad Institute of MIT and Harvard, Cambridge, United States cl Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom cm Headache Unit, Neurology Department, Vall D'Hebron University Hospital, Barcelona, Spain
Publisher Information: Nature Pub. Co
Publication Year: 2016
Collection: Hirsla - Landspítali University Hospital research archive
Subject Terms: Mígreni; Arfgengi; PSY12; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Migraine Disorders/genetics
Description: To access publisher's full text version of this article click on the hyperlink at the bottom of the page ; 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.
Document Type: article in journal/newspaper
Language: English
ISSN: 1546-1718
Relation: http://dx.doi.org/ 10.1038/ng.3598; Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. 2016, 48 (8):856-66 Nat. Genet.; http://hdl.handle.net/2336/618629; Nature genetics
DOI: 10.1038/ng.3598
Availability: http://hdl.handle.net/2336/618629; https://doi.org/10.1038/ng.3598
Rights: Archived with thanks to Nature genetics ; Closed - Lokað
Accession Number: edsbas.EC9C4DF5
Database: BASE