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

[No Value] Evangelou E, [No Value] Valdes AM, [No Value] Kerkhof HJ, U Styrkarsdottir, YY Zhu, I Meulenbelt, RJ Lories, FB Karassa, P Tylzanowski, SD Bos, T ArcOGEN Consortium, Akune,, NK Arden, A Carr, K Chapman, LA Cupples, J Dai, P Deloukas, M Doherty, S Doherty, G EngstromA Gonzalez, BV Halldorsson, CL Hammond, DJ Hart, H Helgadottir, A Hofman, S Ikegawa, T Ingvarsson, Q Jiang, H Jonsson, J Kaprio, H Kawaguchi, K Kisand, M Kloppenburg, UM Kujala, LS Lohmander, J Loughlin, FP Luyten, A Mabuchi, A McCaskie, M Nakajima, PM Nilsson, N Nishida, WER Ollier, K Panoutsopoulou, T van de Putte, SH Ralston, F Rivadeneira, J Saarela, S Schulte-Merker, D Shi, PE Slagboom, A Sudo, A Tamm, An Tamm, G Thorleifsson, U Thorsteinsdottir, A Tsezou, Ga Wallis, JM Wilkinson, N Yoshimura, E Zeggini, G Zhai, F Zhang, I Jonsdottir, AG Uitterlinden, DT Felson, JB van Meurs, K Stefansson, JPA Ioannidis, TD Spector

Research output: Contribution to journalArticle (Academic Journal)peer-review

99 Citations (Scopus)

Abstract

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.
Translated title of the contributionMeta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
Original languageEnglish
Pages (from-to)349 - 355
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume70 (2)
DOIs
Publication statusPublished - Feb 2011

Bibliographical note

Other: One of the authors is Translation Research in Europe Applied Technologies for Osteoarthritis (TreatOA)

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