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

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

Annals of the Rheumatic Diseases. 2011;70(2):349-355.

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Abstract

OBJECTIVES: /st> 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: /st> 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: /st> 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: /st> 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.

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Volume:
70
Issue:
2
Pagination:
349-355
Digital Object Identifier:
10.1136/ard.2010.132787
Pubmed Identifier:
21068099
Pii Identifier:
ard.2010.132787
Access state:
Active

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Record metadata

Manchester eScholar ID:
uk-ac-man-scw:96110
Created by:
Hookway, Sue
Created:
25th November, 2010, 08:45:43
Last modified by:
Hookway, Sue
Last modified:
20th July, 2015, 12:48:10

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