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Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles.
Hautakangas, Heidi; Winsvold, Bendik S; Ruotsalainen, Sanni E; Bjornsdottir, Gyda; Harder, Aster V E; Kogelman, Lisette J A; Thomas, Laurent F; Noordam, Raymond; Benner, Christian; Gormley, Padhraig; Artto, Ville; Banasik, Karina; Bjornsdottir, Anna; Boomsma, Dorret I; Brumpton, Ben M; Burgdorf, Kristoffer Sølvsten; Buring, Julie E; Chalmer, Mona Ameri; de Boer, Irene; Dichgans, Martin; Erikstrup, Christian; Färkkilä, Markus; Garbrielsen, Maiken Elvestad; Ghanbari, Mohsen; Hagen, Knut; Häppölä, Paavo; Hottenga, Jouke-Jan; Hrafnsdottir, Maria G; Hveem, Kristian; Johnsen, Marianne Bakke; Kähönen, Mika; Kristoffersen, Espen S; Kurth, Tobias; Lehtimäki, Terho; Lighart, Lannie; Magnusson, Sigurdur H; Malik, Rainer; Pedersen, Ole Birger; Pelzer, Nadine; Penninx, Brenda W J H; Ran, Caroline; Ridker, Paul M; Rosendaal, Frits R; Sigurdardottir, Gudrun R; Skogholt, Anne Heidi; Sveinsson, Olafur A; Thorgeirsson, Thorgeir E; Ullum, Henrik; Vijfhuizen, Lisanne S; Widén, Elisabeth.
Affiliation
  • Hautakangas H; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
  • Winsvold BS; Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
  • Ruotsalainen SE; K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • Bjornsdottir G; Department of Neurology, Oslo University Hospital, Oslo, Norway.
  • Harder AVE; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
  • Kogelman LJA; deCODE genetics/Amgen Inc., Reykjavik, Iceland.
  • Thomas LF; Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
  • Noordam R; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
  • Benner C; Danish Headache Center, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark.
  • Gormley P; K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • Artto V; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
  • Banasik K; BioCore - Bioinformatics Core Facility, Norwegian University of Science and Technology, Trondheim, Norway.
  • Bjornsdottir A; Clinic of Laboratory Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
  • Boomsma DI; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
  • Brumpton BM; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
  • Burgdorf KS; GlaxoSmithKline, Cambridge, MA, USA.
  • Buring JE; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
  • Chalmer MA; Novo Nordic Foundation Center for Protein Research, Copenhagen University, Copenhagen, Denmark.
  • de Boer I; Neurology Private Practice, Laeknasetrid, Reykjavik, Iceland.
  • Dichgans M; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
  • Erikstrup C; K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • Färkkilä M; Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Garbrielsen ME; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Ghanbari M; Harvard Medical School, Boston, MA, USA.
  • Hagen K; Danish Headache Center, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark.
  • Häppölä P; Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
  • Hottenga JJ; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany.
  • Hrafnsdottir MG; Munich Cluster for Systems Neurology (Synergy), Munich, Germany.
  • Hveem K; Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
  • Johnsen MB; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
  • Kähönen M; K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • Kristoffersen ES; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Kurth T; Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
  • Lehtimäki T; Clinical Research Unit Central Norway, St. Olavs University Hospital, Trondheim, Norway.
  • Lighart L; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
  • Magnusson SH; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
  • Malik R; Landspitali University Hospital, Reykjavik, Iceland.
  • Pedersen OB; K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • Pelzer N; HUNT Research Center, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • Penninx BWJH; K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • Ran C; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Ridker PM; Research and Communication Unit for Musculoskeletal Health (FORMI), Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
  • Rosendaal FR; Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Sigurdardottir GR; Research and Communication Unit for Musculoskeletal Health (FORMI), Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
  • Skogholt AH; Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway.
  • Sveinsson OA; Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
  • Thorgeirsson TE; Institute of Public Health, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Ullum H; Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Vijfhuizen LS; Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
  • Widén E; deCODE genetics/Amgen Inc., Reykjavik, Iceland.
Nat Genet ; 54(2): 152-160, 2022 02.
Article in En | MEDLINE | ID: mdl-35115687
ABSTRACT
Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genetic Predisposition to Disease / Polymorphism, Single Nucleotide / Genome-Wide Association Study / Migraine Disorders Type of study: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2022 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genetic Predisposition to Disease / Polymorphism, Single Nucleotide / Genome-Wide Association Study / Migraine Disorders Type of study: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2022 Document type: Article Affiliation country: