Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22

Evangelos Evangelou; Ana M. Valdes; Hanneke J. M. Kerkhof; Unnur Styrkarsdottir; YanYan Zhu; Ingrid Meulenbelt; Rik J. Lories; Fotini B. Karassa; Przemko Tylzanowski; Steffan D. Bos; Toru Akune; Nigel K. Arden; Andrew Carr; Kay Chapman; L. Adrienne Cupples; Jin Dai; Panos Deloukas; Michael Doherty; Sally Doherty; Gunnar Engstrom; Antonio Gonzalez; Bjarni V. Halldorsson; Christina L. Hammond; Deborah J. Hart; Hafdis Helgadottir; Albert Hofman; Shiro Ikegawa; Thorvaldur Ingvarsson; Qing Jiang; Helgi Jonsson; Jaakko Kaprio; Hiroshi Kawaguchi; Kalle Kisand; Margreet Kloppenburg; Urho M. Kujala; L. Stefan Lohmander; John Loughlin; Frank P. Luyten; Akihiko Mabuchi; Andrew McCaskie; Masahiro Nakajima; Peter M. Nilsson; Nao Nishida; William E. R. Ollier; Kalliope Panoutsopoulou; Tom van de Putte; Stuart H. Ralston; Fernado Rivadeneira; Janna Saarela; Stefan Schulte-Merker; Dongquan Shi; P. Eline Slagboom; Akihiro Sudo; Agu Tamm; Ann Tamm; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Aspasia Tsezou; Gillian A. Wallis; J. Mark Wilkinson; Noriko Yoshimura; Eleftheria Zeggini; Guangju Zhai; Feng Zhang; Ingileif Jonsdottir; Andre G. Uitterlinden; David T. Felson; Joyce B. van Meurs; Kari Stefansson; John P. A. Ioannidis; Timothy D. Spector; ArcOGEN Consortium

doi:10.1136/ard.2010.132787

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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22

Journal article

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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22

Evangelos Evangelou, Ana M. Valdes, Hanneke J. M. Kerkhof, Unnur Styrkarsdottir, YanYan Zhu, Ingrid Meulenbelt, Rik J. Lories, Fotini B. Karassa, Przemko Tylzanowski, Steffan D. Bos, …

Annals of the rheumatic diseases, Vol.70(2), pp.349-355

01/02/2011

DOI: https://doi.org/10.1136/ard.2010.132787

PMCID: PMC3615180

PMID: 21068099

Abstract

Life Sciences & Biomedicine

Rheumatology

Science & Technology

Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.

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Title: Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
Creators - without role: Evangelos Evangelou - University of Ioannina
Ana M. Valdes - Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England
Hanneke J. M. Kerkhof - Erasmus MC
Unnur Styrkarsdottir - deCODE Genet, Reykjavik, Iceland
YanYan Zhu - Boston University
Ingrid Meulenbelt - Netherlands Genom Initiat, Rotterdam, Netherlands
Rik J. Lories - KU Leuven
Fotini B. Karassa - University of Ioannina
Przemko Tylzanowski - KU Leuven
Steffan D. Bos - Netherlands Genom Initiat, Rotterdam, Netherlands
Toru Akune - The University of Tokyo
Nigel K. Arden - Massachusetts Rehabilitation Commission
Andrew Carr - University of Oxford
Kay Chapman - University of Oxford
L. Adrienne Cupples - Boston University
Jin Dai - Nanjing University
Panos Deloukas - Wellcome Sanger Institute
Michael Doherty - University of Nottingham
Sally Doherty - University of Nottingham
Gunnar Engstrom - Lund University
Antonio Gonzalez - Hosp Clin Univ Santiago, Inst Invest Sanitaria, Lab Invest 10, Santiago De Compostela, Spain
Bjarni V. Halldorsson - deCODE Genet, Reykjavik, Iceland
Christina L. Hammond - Hubrecht Inst KNAW, Utrecht, Netherlands
Deborah J. Hart - Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England
Hafdis Helgadottir - deCODE Genet, Reykjavik, Iceland
Albert Hofman - Erasmus MC
Shiro Ikegawa - RIKEN
Thorvaldur Ingvarsson - University of Akureyri
Qing Jiang - Nanjing University
Helgi Jonsson - College Station Medical Center
Jaakko Kaprio - University of Helsinki
Hiroshi Kawaguchi - The University of Tokyo
Kalle Kisand - University of Tartu
Margreet Kloppenburg - Leiden University
Urho M. Kujala - University of Jyväskylä
L. Stefan Lohmander - Lund University
John Loughlin - Newcastle University
Frank P. Luyten - KU Leuven
Akihiko Mabuchi - The University of Tokyo
Andrew McCaskie - Newcastle University
Masahiro Nakajima - RIKEN
Peter M. Nilsson - Lund University
Nao Nishida - The University of Tokyo
William E. R. Ollier - University of Manchester
Kalliope Panoutsopoulou - Wellcome Sanger Institute
Tom van de Putte - TiGenix
Stuart H. Ralston - University of Edinburgh
Fernado Rivadeneira - Erasmus MC
Janna Saarela - University of Helsinki
Stefan Schulte-Merker - Hubrecht Inst KNAW, Utrecht, Netherlands
Dongquan Shi - Nanjing University
P. Eline Slagboom - Netherlands Genom Initiat, Rotterdam, Netherlands
Akihiro Sudo - Mie University
Agu Tamm - University of Tartu
Ann Tamm - University of Tartu
Gudmar Thorleifsson - deCODE Genet, Reykjavik, Iceland
Unnur Thorsteinsdottir - deCODE Genet, Reykjavik, Iceland
Aspasia Tsezou - University of Thessaly
Gillian A. Wallis - University of Manchester
J. Mark Wilkinson - University of Sheffield
Noriko Yoshimura - The University of Tokyo
Eleftheria Zeggini - Wellcome Sanger Institute
Guangju Zhai - Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England
Feng Zhang - Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England
Ingileif Jonsdottir - deCODE Genet, Reykjavik, Iceland
Andre G. Uitterlinden - Erasmus MC
David T. Felson - Boston University
Joyce B. van Meurs - Erasmus MC
Kari Stefansson - deCODE Genet, Reykjavik, Iceland
John P. A. Ioannidis - University of Ioannina
Timothy D. Spector - Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England
ArcOGEN Consortium
Publication Details: Annals of the rheumatic diseases, Vol.70(2), pp.349-355
Publisher: Bmj Publishing Group
Number of pages: 7
Grant note: 18030 / Arthritis Research Campaign (arc); Versus Arthritis G0000934 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) European Community; European Commission 23390361; 21390417; 19109007 / Grants-in-Aid for Scientific Research; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Japan Society for the Promotion of Science; Grants-in-Aid for Scientific Research (KAKENHI) Wellcome Trust Clinical Research Facility at Southampton General Hospital; Wellcome Trust S19109007; B21390417 / apanese Ministry of Education, Culture, Sports, Science and Technology; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) G0901461; G0000934; G0100594; MC_U122886349 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Botnar Foundation Medical Research Council at the Centre for Integrated Genomic Medical Research (CIGMR), University of Manchester; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 2006-1 / Japanese Orthopaedic Association UK NIHR BRC Cavendish Foundation H17-Men-eki-009 / Ministry of Health, Labor and Welfare; Ministry of Health, Labour and Welfare, Japan NHS Foundation Trust in partnership with King's College London 17489 / Versus Arthritis South Yorkshire Clinical Research Network 083948; 068545; WT088885/Z/09/Z; WT079557MA / Wellcome Trust Department of Health via the National Institute for Health Research (NIHR); National Institutes of Health Research (NIHR) Jean Shanks Foundation Flanders Research Foundation (FWO Vlaanderen); FWO Higher Education Funding Council for England; UK Research & Innovation (UKRI); Higher Education Funding Council for England (HEFCE) G0100594; G0000934; MC_U122886349; G0901461 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) UK Blood Services 200800 / European Commission; European Commission Joint Research Centre Collisson Foundation Royal College of Surgeons of England
Identifiers: 9938615708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article