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

E. Evangelou, A.M. Valdes, H.J. Kerkhof, U. Styrkarsdottir, Y. Zhu, I. Meulenbelt, R.J. Lories, F.B. Karassa, P. Tylzanowski, S.D. Bos, T. Akune, N.K. Arden, A. Carr, K. Chapman, L.A. Cupples, J. Dai, P. Deloukas, M. Doherty, S. Doherty, G. EngstromA. Gonzalez, B.V. Halldorsson, C.J. Hammond, D.J. Hart, H. Helgadottir, A. Hofman, S. Ikegawa, T. Ingvarsson, Q. Jiang, H. Jonsson, J. Kaprio, H. Kawaguchi, K. Kisand, M. Kloppenburg, U.M. Kujala, L.S. Lohmander, J. Loughlin, F.P. Luyten, A. Mabuchi, A. McCaskie, M. Nakajima, P.M. Nilsson, N. Nishida, W.E. Ollier, K. Panoutsopoulou, T. van de Putte, S.H. Ralston, F. Rivadeneira, J. Saarela, S. Schulte-Merker, D. Shi, P.E. Slagboom, A. Sudo, A. Tamm, G. Thorleifsson, U. Thorsteinsdottir, A. Tsezou, G.A. Wallis, J.M. Wilkinson, N. Yoshimura, E. Zeggini, G. Zhai, F. Zhang, I. Jonsdottir, A.G. Uitterlinden, D.T. Felson, J.B. van Meurs, K. Stefansson, J.P. Ioannidis, T.D. Spector

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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), 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. [KEYWORDS: Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 7/ genetics, Female, Gene Expression Profiling/methods, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Osteoarthritis, Knee/ genetics, Phenotype, Polymorphism, Single Nucleotide, Young Adult]
Originele taal-2Engels
Pagina's (van-tot)349-355
TijdschriftAnnals of the Rheumatic Diseases
Volume70
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - 2011

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