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Meta-Analysis
. 2011 Feb;70(2):349-55.
doi: 10.1136/ard.2010.132787. Epub 2010 Nov 10.

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

Evangelos Evangelou  1 , Ana M Valdes, Hanneke J M Kerkhof, Unnur Styrkarsdottir, Yanyan Zhu, Ingrid Meulenbelt, Rik J Lories, Fotini B Karassa, Przemko Tylzanowski, Steffan D Bos; arcOGEN Consortium; Toru Akune, Nigel K Arden, Andrew Carr, Kay Chapman, L Adrienne Cupples, Jin Dai, Panos Deloukas, Michael Doherty, Sally Doherty, Gunnar Engstrom, Antonio Gonzalez, Bjarni V Halldorsson, Christina L Hammond, Deborah J Hart, Hafdis Helgadottir, Albert Hofman, Shiro Ikegawa, Thorvaldur Ingvarsson, Qing Jiang, Helgi Jonsson, Jaakko Kaprio, Hiroshi Kawaguchi, Kalle Kisand, Margreet Kloppenburg, Urho M Kujala, L Stefan Lohmander, John Loughlin, Frank P Luyten, Akihiko Mabuchi, Andrew McCaskie, Masahiro Nakajima, Peter M Nilsson, Nao Nishida, William E R Ollier, Kalliope Panoutsopoulou, Tom van de Putte, Stuart H Ralston, Fernado Rivadeneira, Janna Saarela, Stefan Schulte-Merker, Dongquan Shi, P Eline Slagboom, Akihiro Sudo, Agu Tamm, Ann Tamm, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Aspasia Tsezou, Gillian A Wallis, J Mark Wilkinson, Noriko Yoshimura, Eleftheria Zeggini, Guangju Zhai, Feng Zhang, Ingileif Jonsdottir, Andre G Uitterlinden, David T Felson, Joyce B van Meurs, Kari Stefansson, John P A Ioannidis, Timothy D Spector; Translation Research in Europe Applied Technologies for Osteoarthritis (TreatOA)
Affiliations
Meta-Analysis

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

Evangelos Evangelou et al. Ann Rheum Dis. 2011 Feb.

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.

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Figures

Figure 1
Figure 1
Q-Q plot of the expected vs observed distribution of p-values.
Figure 2
Figure 2
Regional association plot of rs4730250. Statistical significance of the associated SNPs are illustrated on –log10 scale. The p-value of the rs4730250 and the other 10 selected SNPs are based on the meta-analysis of all datasets (both GWA studies and replication studies). P-values for the rest of the SNPs are based on the meta-analysis of the GWA studies. The sentinel SNP is shown in blue. The correlation of the sentinel SNP is shown on a scale from minimal (gray) to maximal (red). SNPs in red have r2≥0.8 with the sentinel SNP and SNPs in orange have r2≥ 0.5. Chromosome positions are based on HapMap release 22 build 36.
Figure 3
Figure 3
a) Forest plot of study-specific estimates (black boxes) and summary OR estimates and 95% confidence intervals (95% CIs) (diamond) for the association between the rs4730250 SNP and knee osteoarthritis.
See this image and copyright information in PMC

References

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