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dc.contributor.authorBoer, Cindy G
dc.contributor.authorHatzikotoulas, Konstantinos
dc.contributor.authorSoutham, Lorraine
dc.contributor.authorStefánsdóttir, Lilja
dc.contributor.authorZhang, Yanfei
dc.contributor.authorCoutinho de Almeida, Rodrigo
dc.contributor.authorWu, Tian T
dc.contributor.authorZheng, Jie
dc.contributor.authorHartley, April
dc.contributor.authorTeder-Laving, Maris
dc.contributor.authorSkogholt, Anne Heidi
dc.contributor.authorTerao, Chikashi
dc.contributor.authorZengini, Eleni
dc.contributor.authorAlexiadis, George
dc.contributor.authorBarysenka, Andrei
dc.contributor.authorBjornsdottir, Gyda
dc.contributor.authorGabrielsen, Maiken E
dc.contributor.authorGilly, Arthur
dc.contributor.authorIngvarsson, Thorvaldur
dc.contributor.authorJohnsen, Marianne B
dc.contributor.authorJonsson, Helgi
dc.contributor.authorKloppenburg, Margreet
dc.contributor.authorLuetge, Almut
dc.contributor.authorLund, Sigrun H
dc.contributor.authorMägi, Reedik
dc.contributor.authorMangino, Massimo
dc.contributor.authorNelissen, Rob R G H H
dc.contributor.authorShivakumar, Manu
dc.contributor.authorSteinberg, Julia
dc.contributor.authorTakuwa, Hiroshi
dc.contributor.authorThomas, Laurent F
dc.contributor.authorTuerlings, Margo
dc.contributor.authorBabis, George C
dc.contributor.authorCheung, Jason Pui Yin
dc.contributor.authorKang, Jae Hee
dc.contributor.authorKraft, Peter
dc.contributor.authorLietman, Steven A
dc.contributor.authorSamartzis, Dino
dc.contributor.authorSlagboom, P Eline
dc.contributor.authorStefansson, Kari
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorTobias, Jonathan H
dc.contributor.authorUitterlinden, André G
dc.contributor.authorWinsvold, Bendik
dc.contributor.authorZwart, John-Anker
dc.contributor.authorDavey Smith, George
dc.contributor.authorSham, Pak Chung
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorGaunt, Tom R
dc.contributor.authorMorris, Andrew P
dc.contributor.authorValdes, Ana M
dc.contributor.authorTsezou, Aspasia
dc.contributor.authorCheah, Kathryn S E
dc.contributor.authorIkegawa, Shiro
dc.contributor.authorHveem, Kristian
dc.contributor.authorEsko, Tõnu
dc.contributor.authorWilkinson, J Mark
dc.contributor.authorMeulenbelt, Ingrid
dc.contributor.authorLee, Ming Ta Michael
dc.contributor.authorvan Meurs, Joyce B J
dc.contributor.authorStyrkársdóttir, Unnur
dc.contributor.authorZeggini, Eleftheria
dc.date.accessioned2021-10-14T14:05:08Z
dc.date.available2021-10-14T14:05:08Z
dc.date.issued2021-08-26
dc.date.submitted2021-10
dc.identifier.citationBoer CG, Hatzikotoulas K, Southam L, Stefánsdóttir L, Zhang Y, Coutinho de Almeida R, Wu TT, Zheng J, Hartley A, Teder-Laving M, Skogholt AH, Terao C, Zengini E, Alexiadis G, Barysenka A, Bjornsdottir G, Gabrielsen ME, Gilly A, Ingvarsson T, Johnsen MB, Jonsson H, Kloppenburg M, Luetge A, Lund SH, Mägi R, Mangino M, Nelissen RRGHH, Shivakumar M, Steinberg J, Takuwa H, Thomas LF, Tuerlings M; arcOGEN Consortium; HUNT All-In Pain; ARGO Consortium; Regeneron Genetics Center, Babis GC, Cheung JPY, Kang JH, Kraft P, Lietman SA, Samartzis D, Slagboom PE, Stefansson K, Thorsteinsdottir U, Tobias JH, Uitterlinden AG, Winsvold B, Zwart JA, Davey Smith G, Sham PC, Thorleifsson G, Gaunt TR, Morris AP, Valdes AM, Tsezou A, Cheah KSE, Ikegawa S, Hveem K, Esko T, Wilkinson JM, Meulenbelt I, Lee MTM, van Meurs JBJ, Styrkársdóttir U, Zeggini E. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell. 2021 Sep 2;184(18):4784-4818.e17. doi: 10.1016/j.cell.2021.07.038.en_US
dc.identifier.pmid34450027
dc.identifier.doi10.1016/j.cell.2021.07.038
dc.identifier.urihttp://hdl.handle.net/2336/621900
dc.descriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Downloaden_US
dc.description.abstractOsteoarthritis 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.en_US
dc.description.sponsorshipUK Biobank Resource UK Research & Innovation (UKRI) Medical Research Council UK (MRC) NIHR Nottingham BRC University of Bristol UK Research & Innovation (UKRI) Medical Research Council UK (MRC)en_US
dc.language.isoenen_US
dc.publisherCell Pressen_US
dc.relation.urlhttps://www.sciencedirect.com/science/article/pii/S0092867421009417?via%3Dihuben_US
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459317/en_US
dc.rightsCopyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
dc.subjectdrug targetsen_US
dc.subjecteffector genesen_US
dc.subjectfunctional genomicsen_US
dc.subjectgenetic architectureen_US
dc.subjectgenome-wide association meta-analysisen_US
dc.subjectosteoarthritisen_US
dc.subjectSlitgigten_US
dc.subjectGenen_US
dc.subject.meshOsteoarthritisen_US
dc.subject.meshGenome-Wide Association Studyen_US
dc.titleDeciphering osteoarthritis genetics across 826,690 individuals from 9 populations.en_US
dc.typeArticleen_US
dc.identifier.eissn1097-4172
dc.contributor.department1Department of Internal Medicine, Erasmus MC, Medical Center, 3015CN Rotterdam, the Netherlands. 2Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany. 3deCODE Genetics/Amgen Inc., 102 Reykjavik, Iceland. 4Genomic Medicine Institute, Geisinger Health System, Danville, PA 17822, USA. 5Department of Biomedical Data Sciences, Section Molecular Epidemiology, Postzone S05-P Leiden University Medical Center, 2333ZC Leiden, the Netherlands. 6Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China. 7MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. 8MRC 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. 9Estonian Genome Center, Institute of Genomics, University of Tartu, 51010 Tartu, Estonia. 10K.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. 11Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan. 124(th) Psychiatric Department, Dromokaiteio Psychiatric Hospital, 12461 Athens, Greece. 131(st) Department of Orthopaedics, KAT General Hospital, 14561 Athens, Greece. 14Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland; Department of Orthopedic Surgery, Akureyri Hospital, 600 Akureyri, Iceland. 15K.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 and Communication Unit for Musculoskeletal Health (FORMI), Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, 0424 Oslo, Norway. 16Department of Medicine, Landspitali The National University Hospital of Iceland, 108 Reykjavik, Iceland; Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland. 17Departments of Rheumatology and Clinical Epidemiology, Leiden University Medical Center, 9600, 23OORC Leiden, the Netherlands. 18Department of Twin Research and Genetic Epidemiology, Kings College London, London SE1 7EH, UK. 19Department of Orthopaedics, Leiden University Medical Center, 9600, 23OORC Leiden, the Netherlands. 20Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 21Institute 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. 22Laboratory 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. 23K.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 Trondheim, Norway; BioCore-Bioinformatics Core Facility, Norwegian University of Science and Technology, 7491 Trondheim, Norway; Clinic of Laboratory Medicine, St. Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway. 242(nd) Department of Orthopaedics, National and Kapodistrian University of Athens, Medical School, Nea Ionia General Hospital Konstantopouleio, 14233 Athens, Greece. 25Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong, China. 26Department of Medicine, Brigham and Women's Hospital, 181 Longwood Ave, Boston, MA 02115, USA. 27Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. 28Musculoskeletal Institute, Geisinger Health System, Danville, PA 17822, USA. 29Department 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. 30deCODE Genetics/Amgen Inc., 102 Reykjavik, Iceland; Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland. 31Musculoskeletal 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. 32K.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 Hospital and University of Oslo, 0450 Oslo, Norway; Department of Neurology, Oslo University Hospital, 0424 Oslo, Norway. 33K.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 Hospital and University of Oslo, 0450 Oslo, Norway. 34MRC 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. 35Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China. 36Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, University of Manchester, Manchester M13 9LJ, UK. 37Faculty of Medicine and Health Sciences, School of Medicine, University of Nottingham, Nottingham, Nottinghamshire NG5 1PB, UK. 38Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, Larissa 411 10, Greece. 39School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China. 40Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo 108-8639, Japan. 41K.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; HUNT Research Center, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7600 Levanger, Norway. 42Department of Oncology and Metabolism and Healthy Lifespan Institute, University of Sheffield, Sheffield S10 2RX, UK. 43Genomic Medicine Institute, Geisinger Health System, Danville, PA 17822, USA; Institute of Biomedical Sciences, Academia Sinica, 115 Taipei, Taiwan. 44Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany; TUM School of Medicine, Technical University of Munich and Klinikum Rechts der Isar, 81675 Munich, Germany. Electronic address: eleftheria.zeggini@helmholtz-muenchen.de.en_US
dc.identifier.journalCellen_US
dc.rights.accessOpen Access - Opinn aðganguren_US
dc.departmentcodeNAA12
dc.departmentcodeRHE12
dc.source.journaltitleCell
dc.source.volume184
dc.source.issue18
dc.source.beginpage4784
dc.source.endpage4818.e17
refterms.dateFOA2021-10-14T14:05:08Z
dc.source.countryUnited States


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