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

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

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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιών
Keywords: risk-factors,body-mass,gdf5,hip,classification,heterogeneity,obesity,cohorts,joint,frzb
ISSN: 0003-4967
Link: <Go to ISI>://000286179000022
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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