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Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis.

Author: 1 Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK. 2 5th Psychiatric Department, Dromokaiteio Psychiatric Hospital, Athens, Greece. 3 Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK. 4 GSK, R&D Target Sciences, Medicines Research Centre, Stevenage, UK. 5 Cancer Research Division, Cancer Council NSW, Sydney, New South Wales, Australia. 6 Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil. 7 Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK. 8 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. 9 Departments of Internal Medicine and Epidemiology, Erasmus MC, Rotterdam, the Netherlands. 10 deCODE genetics/Amgen, Reykjavik, Iceland. 11 Department of Orthopaedic Surgery, Akureyri Hospital, Akureyri, Iceland. 12 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 13 Institution of Health Science, University of Akureyri, Akureyri, Iceland. 14 Department of Medicine, Landspitali, National University Hospital of Iceland, Reykjavik, Iceland. 15 2nd Department of Orthopaedic Surgery, Konstantopouleio General Hospital, National and Kapodistrian University of Athens, Athens, Greece. 16 Division of Trauma & Orthopaedic Surgery, Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. 17 Population Health Sciences, University of Bristol, Bristol, UK. 18 National Institute for Health Research, Bristol Biomedical Research Centre, University Hospitals Bristol, NHS Foundation Trust and University of Bristol, Bristol, UK. 19 Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK. eleftheria@sanger.ac.uk.; Zengini, Eleni; Hatzikotoulas, Konstantinos; Tachmazidou, Ioanna; Steinberg, Julia; Hartwig, Fernando P; Southam, Lorraine; Hackinger, Sophie; Boer, Cindy G; Styrkarsdottir, Unnur; Gilly, Arthur; Suveges, Daniel; Killian, Britt; Ingvarsson, Thorvaldur; Jonsson, Helgi; Babis, George C; McCaskie, Andrew; Uitterlinden, Andre G; van Meurs, Joyce B J; Thorsteinsdottir, Unnur; Stefansson, Kari; Davey Smith, George; Wilkinson, Jeremy M; Zeggini, Eleftheria
Publisher: Nature Publishing Group
Edition/Format:   Downloadable article : English
Publication:Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis. 2018, 50 (4):549-558 Nat. Genet.
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All Authors / Contributors: 1 Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK. 2 5th Psychiatric Department, Dromokaiteio Psychiatric Hospital, Athens, Greece. 3 Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK. 4 GSK, R&D Target Sciences, Medicines Research Centre, Stevenage, UK. 5 Cancer Research Division, Cancer Council NSW, Sydney, New South Wales, Australia. 6 Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil. 7 Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK. 8 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. 9 Departments of Internal Medicine and Epidemiology, Erasmus MC, Rotterdam, the Netherlands. 10 deCODE genetics/Amgen, Reykjavik, Iceland. 11 Department of Orthopaedic Surgery, Akureyri Hospital, Akureyri, Iceland. 12 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 13 Institution of Health Science, University of Akureyri, Akureyri, Iceland. 14 Department of Medicine, Landspitali, National University Hospital of Iceland, Reykjavik, Iceland. 15 2nd Department of Orthopaedic Surgery, Konstantopouleio General Hospital, National and Kapodistrian University of Athens, Athens, Greece. 16 Division of Trauma & Orthopaedic Surgery, Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. 17 Population Health Sciences, University of Bristol, Bristol, UK. 18 National Institute for Health Research, Bristol Biomedical Research Centre, University Hospitals Bristol, NHS Foundation Trust and University of Bristol, Bristol, UK. 19 Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK. eleftheria@sanger.ac.uk.; Zengini, Eleni; Hatzikotoulas, Konstantinos; Tachmazidou, Ioanna; Steinberg, Julia; Hartwig, Fernando P; Southam, Lorraine; Hackinger, Sophie; Boer, Cindy G; Styrkarsdottir, Unnur; Gilly, Arthur; Suveges, Daniel; Killian, Britt; Ingvarsson, Thorvaldur; Jonsson, Helgi; Babis, George C; McCaskie, Andrew; Uitterlinden, Andre G; van Meurs, Joyce B J; Thorsteinsdottir, Unnur; Stefansson, Kari; Davey Smith, George; Wilkinson, Jeremy M; Zeggini, Eleftheria
OCLC Number: 1044753008
Language Note: English

Abstract:

To access publisher's full text version of this article click on the hyperlink below

Osteoarthritis is a common complex disease imposing a large public-health burden. Here, we performed a genome-wide association study for osteoarthritis, using data across 16.5 million variants from the UK Biobank resource. After performing replication and meta-analysis in up to 30,727 cases and 297,191 controls, we identified nine new osteoarthritis loci, in all of which the most likely causal variant was noncoding. For three loci, we detected association with biologically relevant radiographic endophenotypes, and in five signals we identified genes that were differentially expressed in degraded compared with intact articular cartilage from patients with osteoarthritis. We established causal effects on osteoarthritis for higher body mass index but not for triglyceride levels or genetic predisposition to type 2 diabetes.

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