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Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.
Boer, Cindy G; Hatzikotoulas, Konstantinos; Southam, Lorraine; Stefánsdóttir, Lilja; Zhang, Yanfei; Coutinho de Almeida, Rodrigo; Wu, Tian T; Zheng, Jie; Hartley, April; Teder-Laving, Maris; Skogholt, Anne Heidi; Terao, Chikashi; Zengini, Eleni; Alexiadis, George; Barysenka, Andrei; Bjornsdottir, Gyda; Gabrielsen, Maiken E; Gilly, Arthur; Ingvarsson, Thorvaldur; Johnsen, Marianne B; Jonsson, Helgi; Kloppenburg, Margreet; Luetge, Almut; Lund, Sigrun H; Mägi, Reedik; Mangino, Massimo; Nelissen, Rob R G H H; Shivakumar, Manu; Steinberg, Julia; Takuwa, Hiroshi; Thomas, Laurent F; Tuerlings, Margo; Babis, George C; Cheung, Jason Pui Yin; Kang, Jae Hee; Kraft, Peter; Lietman, Steven A; Samartzis, Dino; Slagboom, P Eline; Stefansson, Kari; Thorsteinsdottir, Unnur; Tobias, Jonathan H; Uitterlinden, André G; Winsvold, Bendik; Zwart, John-Anker; Davey Smith, George; Sham, Pak Chung; Thorleifsson, Gudmar; Gaunt, Tom R; Morris, Andrew P.
Afiliação
  • Boer CG; Department of Internal Medicine, Erasmus MC, Medical Center, 3015CN Rotterdam, the Netherlands.
  • Hatzikotoulas K; Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Southam L; Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Stefánsdóttir L; deCODE Genetics/Amgen Inc., 102 Reykjavik, Iceland.
  • Zhang Y; Genomic Medicine Institute, Geisinger Health System, Danville, PA 17822, USA.
  • Coutinho de Almeida R; Department of Biomedical Data Sciences, Section Molecular Epidemiology, Postzone S05-P Leiden University Medical Center, 2333ZC Leiden, the Netherlands.
  • Wu TT; Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
  • Zheng J; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
  • Hartley A; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK; Musculoskeletal Research Unit, Translation Health Sciences, Bristol Medical School, University of Bristol, Southmead Hospital, Bristol BS10 5NB, UK.
  • Teder-Laving M; Estonian Genome Center, Institute of Genomics, University of Tartu, 51010 Tartu, Estonia.
  • Skogholt AH; 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, 7491 Trondheim, Norway.
  • Terao C; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan.
  • Zengini E; 4(th) Psychiatric Department, Dromokaiteio Psychiatric Hospital, 12461 Athens, Greece.
  • Alexiadis G; 1(st) Department of Orthopaedics, KAT General Hospital, 14561 Athens, Greece.
  • Barysenka A; Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Bjornsdottir G; deCODE Genetics/Amgen Inc., 102 Reykjavik, Iceland.
  • Gabrielsen ME; 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, 7491 Trondheim, Norway.
  • Gilly A; Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Ingvarsson T; Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland; Department of Orthopedic Surgery, Akureyri Hospital, 600 Akureyri, Iceland.
  • Johnsen MB; 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, 7491 Trondheim, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0316 Oslo, Norway; Research
  • Jonsson H; Department of Medicine, Landspitali The National University Hospital of Iceland, 108 Reykjavik, Iceland; Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
  • Kloppenburg M; Departments of Rheumatology and Clinical Epidemiology, Leiden University Medical Center, 9600, 23OORC Leiden, the Netherlands.
  • Luetge A; 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, 7491 Trondheim, Norway.
  • Lund SH; deCODE Genetics/Amgen Inc., 102 Reykjavik, Iceland.
  • Mägi R; Estonian Genome Center, Institute of Genomics, University of Tartu, 51010 Tartu, Estonia.
  • Mangino M; Department of Twin Research and Genetic Epidemiology, Kings College London, London SE1 7EH, UK.
  • Nelissen RRGHH; Department of Orthopaedics, Leiden University Medical Center, 9600, 23OORC Leiden, the Netherlands.
  • Shivakumar M; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Steinberg J; Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany; Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW 1340, Australia.
  • Takuwa H; Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo 108-8639, Japan; Department of Orthopedic Surgery, Shimane University, Shimane 693-8501, Japan.
  • Thomas LF; 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, 7491 Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 T
  • Tuerlings M; Department of Biomedical Data Sciences, Section Molecular Epidemiology, Postzone S05-P Leiden University Medical Center, 2333ZC Leiden, the Netherlands.
  • Babis GC; 2(nd) Department of Orthopaedics, National and Kapodistrian University of Athens, Medical School, Nea Ionia General Hospital Konstantopouleio, 14233 Athens, Greece.
  • Cheung JPY; Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong, China.
  • Kang JH; Department of Medicine, Brigham and Women's Hospital, 181 Longwood Ave, Boston, MA 02115, USA.
  • Kraft P; Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
  • Lietman SA; Musculoskeletal Institute, Geisinger Health System, Danville, PA 17822, USA.
  • Samartzis D; Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong, China; Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA.
  • Slagboom PE; Department of Biomedical Data Sciences, Section Molecular Epidemiology, Postzone S05-P Leiden University Medical Center, 2333ZC Leiden, the Netherlands.
  • Stefansson K; deCODE Genetics/Amgen Inc., 102 Reykjavik, Iceland; Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
  • Thorsteinsdottir U; deCODE Genetics/Amgen Inc., 102 Reykjavik, Iceland; Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
  • Tobias JH; Musculoskeletal Research Unit, Translation Health Sciences, Bristol Medical School, University of Bristol, Southmead Hospital, Bristol BS10 5NB, UK; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
  • Uitterlinden AG; Department of Internal Medicine, Erasmus MC, Medical Center, 3015CN Rotterdam, the Netherlands.
  • Winsvold B; 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, 7491 Trondheim, Norway; Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University
  • Zwart JA; 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, 7491 Trondheim, Norway; Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University
  • Davey Smith G; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK.
  • Sham PC; Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
  • Thorleifsson G; deCODE Genetics/Amgen Inc., 102 Reykjavik, Iceland.
  • Gaunt TR; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
  • Morris AP; Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, University of Manchester, Manchester M13 9LJ, UK.
Cell ; 184(18): 4784-4818.e17, 2021 09 02.
Article em En | MEDLINE | ID: mdl-34450027
ABSTRACT
Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Osteoartrite / Predisposição Genética para Doença / Genética Populacional Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Osteoartrite / Predisposição Genética para Doença / Genética Populacional Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Holanda