A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

Evangelou, Evangelos, Kerkhos, Hanneke J., Styrkarsdottir, Unnur, Ntzani, Evangelia E., Bos, Steffan D., Esko, Tonu, Evans, Daniel S., Metrustry, Sarah, Panoutsopoulou, Kalliope, Ramos, Yolande F. M., Thorleifsson, Gudmar, Tsilides, Konstantinos K., arcOGEN Consortium, Arden, Nigel, Aslam, Nadim, Bellamy, Nicholas, Birrell, Fraser, Blanco, Francisco J., Carr, Andrew, Chapman, Kay, Day-Williams, Aaron G., Deloukas, Panos, Doherty, Michael, Engstrom, Gunnar, Helgadottir, Hafdis T., Hoffman, Albert, Ingvarsson, Thorvaldur, Jonsson, Helgi, Keis, Aime, Keurentjes, J. Christiaan, Kloppenburg, Margreet, Lind, Penelope A., McCaskie, Andrew, Martin, Nicholas G., Milani, Lili, Montgomery, Grant W., Nelissen, Rob G. H. H., Nevitt, Michael C., Nilsson, Peter M., Ollier, William E. R., Parimi, Netta, Rai, Ashok, Ralston, Stuart H., Reed, Mike R., Riancho, Jose A., Rivadeneira, Fernando, Rodriquez-Fontenla, Christina, Southam, Lorraine, Thorsteinsdottir, Unnar, Tsezou, Aspasia, Wallis, Gillian A., Wilkinson, J. Mark, Gonzales, Antonio, Lane, Nancy E., Lohmander, L. Stefan, Loughlin, John, Metspalu, Andres, Uitterlinden, Andre G., Jonsdottir, Ingileif, Steffansson, Karl, Slagboom, P. Eline, Zeggini, Eleftheria, Meulenbelt, Ingrid, Ioannidis, John P. A., Spector, Tim D., van Meurs, Joyce B. J. and Valdes, Anna M. (2013) A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip. Annals of the Rheumatic Diseases, Online First 1-7. doi:10.1136/annrheumdis-2012-203114

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Author Evangelou, Evangelos
Kerkhos, Hanneke J.
Styrkarsdottir, Unnur
Ntzani, Evangelia E.
Bos, Steffan D.
Esko, Tonu
Evans, Daniel S.
Metrustry, Sarah
Panoutsopoulou, Kalliope
Ramos, Yolande F. M.
Thorleifsson, Gudmar
Tsilides, Konstantinos K.
arcOGEN Consortium
Arden, Nigel
Aslam, Nadim
Bellamy, Nicholas
Birrell, Fraser
Blanco, Francisco J.
Carr, Andrew
Chapman, Kay
Day-Williams, Aaron G.
Deloukas, Panos
Doherty, Michael
Engstrom, Gunnar
Helgadottir, Hafdis T.
Hoffman, Albert
Ingvarsson, Thorvaldur
Jonsson, Helgi
Keis, Aime
Keurentjes, J. Christiaan
Kloppenburg, Margreet
Lind, Penelope A.
McCaskie, Andrew
Martin, Nicholas G.
Milani, Lili
Montgomery, Grant W.
Nelissen, Rob G. H. H.
Nevitt, Michael C.
Nilsson, Peter M.
Ollier, William E. R.
Parimi, Netta
Rai, Ashok
Ralston, Stuart H.
Reed, Mike R.
Riancho, Jose A.
Rivadeneira, Fernando
Rodriquez-Fontenla, Christina
Southam, Lorraine
Thorsteinsdottir, Unnar
Tsezou, Aspasia
Wallis, Gillian A.
Wilkinson, J. Mark
Gonzales, Antonio
Lane, Nancy E.
Lohmander, L. Stefan
Loughlin, John
Metspalu, Andres
Uitterlinden, Andre G.
Jonsdottir, Ingileif
Steffansson, Karl
Slagboom, P. Eline
Zeggini, Eleftheria
Meulenbelt, Ingrid
Ioannidis, John P. A.
Spector, Tim D.
van Meurs, Joyce B. J.
Valdes, Anna M.
Total Author Count Override 67
Title A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
Journal name Annals of the Rheumatic Diseases   Check publisher's open access policy
ISSN 0003-4967
1468-2060
Publication date 2013-08-29
Sub-type Article (original research)
DOI 10.1136/annrheumdis-2012-203114
Open Access Status
Volume Online First
Start page 1
End page 7
Total pages 7
Place of publication London, United Kingdom
Publisher B M J Group
Collection year 2014
Language eng
Formatted abstract
Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects.

Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for ‘in silico’ or ‘de novo’ replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used.

Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10−9 and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10−8) and follow-up studies (p=7.3×10−4). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10−7, OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10−6, OR=1.27 in male specific analysis).

Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published Online First 29 August 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Health and Rehabilitation Sciences Publications
School of Medicine Publications
 
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Created: Wed, 09 Oct 2013, 15:08:24 EST by Chesne McGrath on behalf of National Research on Disability and Rehabilitation Medicine