TY - JOUR T1 - Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22 JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 349 LP - 355 DO - 10.1136/ard.2010.132787 VL - 70 IS - 2 AU - Evangelos Evangelou AU - Ana M Valdes AU - Hanneke J M Kerkhof AU - Unnur Styrkarsdottir AU - YanYan Zhu AU - Ingrid Meulenbelt AU - Rik J Lories AU - Fotini B Karassa AU - Przemko Tylzanowski AU - Steffan D Bos AU - arcOGEN Consortium AU - Toru Akune AU - Nigel K Arden AU - Andrew Carr AU - Kay Chapman AU - L Adrienne Cupples AU - Jin Dai AU - Panos Deloukas AU - Michael Doherty AU - Sally Doherty AU - Gunnar Engstrom AU - Antonio Gonzalez AU - Bjarni V Halldorsson AU - Christina L Hammond AU - Deborah J Hart AU - Hafdis Helgadottir AU - Albert Hofman AU - Shiro Ikegawa AU - Thorvaldur Ingvarsson AU - Qing Jiang AU - Helgi Jonsson AU - Jaakko Kaprio AU - Hiroshi Kawaguchi AU - Kalle Kisand AU - Margreet Kloppenburg AU - Urho M Kujala AU - L Stefan Lohmander AU - John Loughlin AU - Frank P Luyten AU - Akihiko Mabuchi AU - Andrew McCaskie AU - Masahiro Nakajima AU - Peter M Nilsson AU - Nao Nishida AU - William E R Ollier AU - Kalliope Panoutsopoulou AU - Tom van de Putte AU - Stuart H Ralston AU - Fernado Rivadeneira AU - Janna Saarela AU - Stefan Schulte-Merker AU - Dongquan Shi AU - P Eline Slagboom AU - Akihiro Sudo AU - Agu Tamm AU - Ann Tamm AU - Gudmar Thorleifsson AU - Unnur Thorsteinsdottir AU - Aspasia Tsezou AU - Gillian A Wallis AU - J Mark Wilkinson AU - Noriko Yoshimura AU - Eleftheria Zeggini AU - Guangju Zhai AU - Feng Zhang AU - Ingileif Jonsdottir AU - Andre G Uitterlinden AU - David T Felson AU - Joyce B van Meurs AU - Kari Stefansson AU - John P A Ioannidis AU - Timothy D Spector AU - Translation Research in Europe Applied Technologies for Osteoarthritis (TreatOA) Y1 - 2011/02/01 UR - http://ard.bmj.com/content/70/2/349.abstract N2 - 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=9.2×10−9), 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, β), 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. ER -