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Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.
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; 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.
Afiliação
  • Gormley P; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Anttila V; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Winsvold BS; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Palta P; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
  • Esko T; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Pers TH; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Farh KH; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Cuenca-Leon E; FORMI, Oslo University Hospital, Oslo, Norway.
  • Muona M; Department of Neurology, Oslo University Hospital, Oslo, Norway.
  • Furlotte NA; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Kurth T; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Ingason A; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • McMahon G; Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Ligthart L; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.
  • Terwindt GM; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Kallela M; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.
  • Freilinger TM; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
  • Ran C; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
  • Gordon SG; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Stam AH; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Steinberg S; Illumina, San Diego, California, USA.
  • Borck G; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Koiranen M; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Quaye L; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Adams HH; Pediatric Neurology, Vall d'Hebron Research Institute, Barcelona, Spain.
  • Lehtimäki T; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Sarin AP; Folkhälsan Institute of Genetics, Helsinki, Finland.
  • Wedenoja J; Neuroscience Center, University of Helsinki, Helsinki, Finland.
  • Hinds DA; Molecular Neurology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
  • Buring JE; 23andMe, Inc., Mountain View, California, USA.
  • Schürks M; Institute of Public Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Ridker PM; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • Hrafnsdottir MG; deCODE Genetics, Reykjavik, Iceland.
  • Stefansson H; Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Ring SM; Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
  • Hottenga JJ; Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
  • Penninx BW; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
  • Färkkilä M; Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
  • Artto V; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.
  • Kaunisto M; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Vepsäläinen S; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Malik R; Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
  • Heath AC; deCODE Genetics, Reykjavik, Iceland.
  • Madden PA; Institute of Human Genetics, Ulm University, Ulm, Germany.
  • Martin NG; Center for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland.
  • Montgomery GW; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • Kurki MI; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Kals M; Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Mägi R; Department of Clinical Chemistry, Fimlab Laboratories, School of Medicine, University of Tampere, Tampere, Finland.
  • Pärn K; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Nat Genet ; 48(8): 856-66, 2016 08.
Article em En | MEDLINE | ID: mdl-27322543
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Marcadores Genéticos / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Loci Gênicos / Transtornos de Enxaqueca Tipo de estudo: Observational_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Marcadores Genéticos / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Loci Gênicos / Transtornos de Enxaqueca Tipo de estudo: Observational_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos