Title: Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
Authors: Evangelou, Evangelos ×
Valdes, Ana M
Kerkhof, Hanneke J M
Styrkarsdottir, Unnur
Zhu, Yanyan
Meulenbelt, Ingrid
Lories, Rik
Karassa, Fotini B
Tylzanowski, Przemyslaw
Bos, Steffan D
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
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 #
Issue Date: Feb-2011
Publisher: H.K. Lewis
Series Title: Annals of the Rheumatic Diseases vol:70 issue:2 pages:349-355
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.
ISSN: 0003-4967
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Rheumatology Section (-)
× corresponding author
# (joint) last author

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