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

Autor: Gormley P; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Anttila V; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Winsvold BS; FORMI, Oslo University Hospital, Oslo, Norway.; Department of Neurology, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Palta P; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland., Esko T; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Estonian Genome Center, University of Tartu, Tartu, Estonia.; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA., Pers TH; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark., Farh KH; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Illumina, San Diego, California, USA., Cuenca-Leon E; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Pediatric Neurology, Vall d'Hebron Research Institute, Barcelona, Spain., Muona M; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.; Folkhälsan Institute of Genetics, Helsinki, Finland.; Neuroscience Center, University of Helsinki, Helsinki, Finland.; Molecular Neurology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland., Furlotte NA; 23andMe, Inc., Mountain View, California, USA., Kurth T; Institute of Public Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA., Ingason A; deCODE Genetics, Reykjavik, Iceland., McMahon G; Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK., Ligthart L; Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands., Terwindt GM; Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands., Kallela M; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland., Freilinger TM; Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany., Ran C; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden., Gordon SG; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Stam AH; Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands., Steinberg S; deCODE Genetics, Reykjavik, Iceland., Borck G; Institute of Human Genetics, Ulm University, Ulm, Germany., Koiranen M; Center for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland., Quaye L; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Adams HH; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.; Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands., Lehtimäki T; Department of Clinical Chemistry, Fimlab Laboratories, School of Medicine, University of Tampere, Tampere, Finland., Sarin AP; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland., Wedenoja J; Department of Public Health, University of Helsinki, Helsinki, Finland., Hinds DA; 23andMe, Inc., Mountain View, California, USA., Buring JE; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA., Schürks M; Department of Neurology, University Duisburg-Essen, Essen, Germany., Ridker PM; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA., Hrafnsdottir MG; Landspitali University Hospital, Reykjavik, Iceland., Stefansson H; deCODE Genetics, Reykjavik, Iceland., Ring SM; Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK., Hottenga JJ; Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands., Penninx BW; Department of Psychiatry, VU University Medical Centre, Amsterdam, the Netherlands., Färkkilä M; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland., Artto V; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland., Kaunisto M; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland., Vepsäläinen S; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland., Malik R; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany., Heath AC; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA., Madden PA; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA., Martin NG; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Montgomery GW; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Kurki MI; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.; Department of Neurosurgery, NeuroCenter, Kuopio University Hospital, Kuopio, Finland., Kals M; Estonian Genome Center, University of Tartu, Tartu, Estonia., Mägi R; Estonian Genome Center, University of Tartu, Tartu, Estonia., Pärn K; Estonian Genome Center, University of Tartu, Tartu, Estonia., Hämäläinen E; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland., Huang H; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Byrnes AE; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Franke L; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Huang J; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK., Stergiakouli E; Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK., Lee PH; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Sandor C; MRC Functional Genomics Unit, Department of Physiology, Anatomy &Genetics, Oxford University, Oxford, UK., Webber C; MRC Functional Genomics Unit, Department of Physiology, Anatomy &Genetics, Oxford University, Oxford, UK., Cader Z; Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.; Oxford Headache Centre, John Radcliffe Hospital, Oxford, UK., Muller-Myhsok B; Max Planck Institute of Psychiatry, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.; Institute of Translational Medicine, University of Liverpool, Liverpool, UK., Schreiber S; Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany., Meitinger T; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.; Institute of Human Genetics, Technische Universität München, Munich, Germany., Eriksson JG; Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; National Institute for Health and Welfare, Helsinki, Finland., Salomaa V; National Institute for Health and Welfare, Helsinki, Finland., Heikkilä K; Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland., Loehrer E; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Uitterlinden AG; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands., Hofman A; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands., van Duijn CM; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands., Cherkas L; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Pedersen LM; FORMI, Oslo University Hospital, Oslo, Norway., Stubhaug A; Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway.; Medical Faculty, University of Oslo, Oslo, Norway., Nielsen CS; Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway.; Department of Ageing and Health, Norwegian Institute of Public Health, Oslo, Norway., Männikkö M; Center for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland., Mihailov E; Estonian Genome Center, University of Tartu, Tartu, Estonia., Milani L; Estonian Genome Center, University of Tartu, Tartu, Estonia., Göbel H; Kiel Pain and Headache Center, Kiel, Germany., Esserlind AL; Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark., Christensen AF; Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark., Hansen TF; Institute of Biological Psychiatry, Mental Health Center Sct. Hans, University of Copenhagen, Roskilde, Denmark., Werge T; Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Copenhagen, Denmark.; Institute of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Copenhagen, Copenhagen, Denmark.; iPSYCH-The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark., Kaprio J; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.; Department of Public Health, University of Helsinki, Helsinki, Finland.; Department of Health, National Institute for Health and Welfare, Helsinki, Finland., Aromaa AJ; National Institute for Health and Welfare, Helsinki, Finland., Raitakari O; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland., Ikram MA; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.; Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands.; Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands., Spector T; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Järvelin MR; Center for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland.; Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; Biocenter Oulu, University of Oulu, Oulu, Finland.; Unit of Primary Care, Oulu University Hospital, Oulu, Finland., Metspalu A; Estonian Genome Center, University of Tartu, Tartu, Estonia., Kubisch C; Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Strachan DP; Population Health Research Institute, St George's, University of London, London, UK., Ferrari MD; Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands., Belin AC; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden., Dichgans M; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Wessman M; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.; Folkhälsan Institute of Genetics, Helsinki, Finland., van den Maagdenberg AM; Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.; Department of Human Genetics, Leiden University Medical Centre, Leiden, the Netherlands., Zwart JA; FORMI, Oslo University Hospital, Oslo, Norway.; Department of Neurology, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Boomsma DI; Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands., Smith GD; Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK., Stefansson K; deCODE Genetics, Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Eriksson N; 23andMe, Inc., Mountain View, California, USA., Daly MJ; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Neale BM; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Olesen J; Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark., Chasman DI; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA., Nyholt DR; Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia., Palotie A; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2016 Aug; Vol. 48 (8), pp. 856-66. Date of Electronic Publication: 2016 Jun 20.
DOI: 10.1038/ng.3598
Abstrakt: 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.
Databáze: MEDLINE