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 EngstromAntonio 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

Research output: Contribution to journalArticlepeer-review

113 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)349 - 355
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume70
Issue number2
DOIs
Publication statusPublished - Feb 2011

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