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

Evangelou, E. and Valdes, A. M. and Kerkhof, H. J. and Styrkarsdottir, U. and Zhu, Y. and Meulenbelt, I. and Lories, R. J. and Karassa, F. B. and Tylzanowski, P. and Bos, S. D. and Akune, T. and Arden, N. K. and Carr, A. and Chapman, K. and Cupples, L. A. and Dai, J. and Deloukas, P. and Doherty, M. and Doherty, S. and Engstrom, G. and Gonzalez, A. and Halldorsson, B. V. and Hammond, C.J. and Hart, D. J. and Helgadottir, H. and Hofman, A. and Ikegawa, S. and Ingvarsson, T. and Jiang, Q. and Jonsson, H. and Kaprio, J. and Kawaguchi, H. and Kisand, K. and Kloppenburg, M. and Kujala, U. M. and Lohmander, L. S. and Loughlin, J. and Luyten, F. P. and Mabuchi, A. and McCaskie, A. and Nakajima, M. and Nilsson, P. M. and Nishida, N. and Ollier, W. E. and Panoutsopoulou, K. and Putte van de, T. and Ralston, S. H. and Rivadeneira, F. and Saarela, J. and Schulte-Merker, S. and Shi, D. and Slagboom, P. E. and Sudo, A. and Tamm, A. and Thorleifsson, G. and Thorsteinsdottir, U. and Tsezou, A. and Wallis, G. A. and Wilkinson, J. M. and Yoshimura, N. and Zeggini, E. and Zhai, G. and Zhang, F. and Jonsdottir, I. and Uitterlinden, A.G. and Felson, D. T. and Meurs van, J. B. and Stefansson, K. and Ioannidis, J. P. and Spector, T.D. (2010) Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22. Annals of the Rheumatic Diseases. ISSN 0003-4967.

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Official URL: http://dx.doi.org/10.1136/ard.2010.132787

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=9.2x10(-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, 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.

Item Type:Article
Institutes:Hubrecht Instituut
ID Code:9523
Deposited On:07 Feb 2011 01:00
Last Modified:07 Sep 2011 17:01

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