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- DOI: 10.1002/art.38300
- PMID: 24338622
- UKPMCID: 24338622
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Assessment of osteoarthritis candidate genes in a meta-analysis of 9 genome-wide association studies.
Rodriguez-Fontenla, Cristina; Calaza, Manuel; Esko, Tõnu; Garces, Carlos M; Gomez-Reino, Juan J; Helgadottir, Hafdis; Hofman, Albert; Jonsdottir, Ingileif; Kerkhof, Hanneke J M; Kloppenburg, Margreet; McCaskie, Andrew; Ntzani, Evangelia E; Evangelou, Evangelos; Ollier, William E R; Oreiro, Natividad; Panoutsopoulou, Kalliope; Ralston, Stuart H; Ramos, Yolande F; Riancho, Jose A; Rivadeneira, Fernando; Slagboom, P Eline; Styrkarsdottir, Unnur; Thorsteinsdottir, Unnur; Valdes, Ana M; Thorleifsson, Gudmar; Tsezou, Aspasia; Uitterlinden, André G; Wallis, Gillian A; Wilkinson, J Mark; Zhai, Guangju; Zhu, Yanyan; arcOGEN_Consortium; Felson, David T; Ioannidis, John P A; Arden, Nigel; Loughlin, John; Metspalu, Andres; Meulenbelt, Ingrid; Stefansson, Kari; van Meurs, Joyce B; Zeggini, Eleftheria; Spector, Timothy D; Gonzalez, Antonio; Blanco, Francisco J; Carr, Andrew; Chapman, Kay; Deloukas, Panos; Doherty, Michael
Arthritis and rheumatism. 2014;66(4):940-949.
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Full-text held externally
- DOI: 10.1002/art.38300
- PMID: 24338622
- UKPMCID: 24338622
Abstract
Objectives: To assess osteoarthritis (OA) candidate genes for identification of promising genetic factors and, secondarily, to assess the candidate gene approach in OA. Methods: 199 published candidate genes for OA were obtained from the HuGe Navigator. All their SNPs with allele frequency >5% were assessed with fixed effect meta-analysis of 9 genome-wide association studies (GWAS) including 5 636 knee OA patients and 16 972 controls, and 4 349 hip OA patients and 17 836 controls of European ancestry. Additional 5 921 individuals were studied for top SNPs in the meta-analysis. Significance was corrected for the number of independent tests at p < 1.58 x 10(-5) . Results: SNPs at only two of the 199 candidate genes were associated with OA in the meta-analysis. They were associated with hip OA, COL11A1 showing two independent associations in the combined analysis (rs4907986, p = 1.29 x 10(-5) , OR = 1.12; 95 % CI = 1.06-1.17; and rs1241164, p = 1.47 x 10(-5) , OR = 0.82, CI = 0.74-0.89) and a SNP in linkage disequilibrium with rs4907986 in the female-specific analysis (rs4908291, p = 1.29 x 10(-5) , OR = 0.87, CI = 0.82-0.92), and VEGF associated in male-specific analysis (rs833058, p = 1.35 x 10(-5) , OR = 0.85, CI = 0.79-0.91). After genotyping additional samples, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened. Conclusion: Two candidate genes were significantly associated with OA in this focused meta-analysis COL11A1 and VEGF. The remaining candidate genes were not associated. © 2013 American College of Rheumatology.
Bibliographic metadata
- Rodriguez-Fontenla, Cristina
- Calaza, Manuel
- Esko, Tõnu
- Garces, Carlos M
- Gomez-Reino, Juan J
- Helgadottir, Hafdis
- Hofman, Albert
- Jonsdottir, Ingileif
- Kerkhof, Hanneke J M
- Kloppenburg, Margreet
- McCaskie, Andrew
- Ntzani, Evangelia E
- Evangelou, Evangelos
- Ollier, William E R
- Oreiro, Natividad
- Panoutsopoulou, Kalliope
- Ralston, Stuart H
- Ramos, Yolande F
- Riancho, Jose A
- Rivadeneira, Fernando
- Slagboom, P Eline
- Styrkarsdottir, Unnur
- Thorsteinsdottir, Unnur
- Valdes, Ana M
- Thorleifsson, Gudmar
- Tsezou, Aspasia
- Uitterlinden, André G
- Wallis, Gillian A
- Wilkinson, J Mark
- Zhai, Guangju
- Zhu, Yanyan
- arcOGEN_Consortium
- Felson, David T
- Ioannidis, John P A
- Arden, Nigel
- Loughlin, John
- Metspalu, Andres
- Meulenbelt, Ingrid
- Stefansson, Kari
- van Meurs, Joyce B
- Zeggini, Eleftheria
- Spector, Timothy D
- Gonzalez, Antonio
- Blanco, Francisco J
- Carr, Andrew
- Chapman, Kay
- Deloukas, Panos
- Doherty, Michael