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Assessment of Osteoarthritis Candidate Genes in a Meta-Analysis of Nine Genome-Wide Association Studies
OBJECTIVE: To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. METHODS: A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) N...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660891/ https://www.ncbi.nlm.nih.gov/pubmed/24757145 http://dx.doi.org/10.1002/art.38300 |
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author | Rodriguez-Fontenla, Cristina Calaza, Manuel Evangelou, Evangelos Valdes, Ana M Arden, Nigel Blanco, Francisco J Carr, Andrew Chapman, Kay Deloukas, Panos Doherty, Michael Esko, Tõnu Garcés Aletá, Carlos M Gomez-Reino Carnota, Juan J Helgadottir, Hafdis Hofman, Albert Jonsdottir, Ingileif Kerkhof, Hanneke J M Kloppenburg, Margreet McCaskie, Andrew Ntzani, Evangelia E 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 Thorleifsson, Gudmar Tsezou, Aspasia Uitterlinden, André G Wallis, Gillian A Wilkinson, J Mark Zhai, Guangju Zhu, Yanyan Felson, David T Ioannidis, John P A Loughlin, John Metspalu, Andres Meulenbelt, Ingrid Stefansson, Kari van Meurs, Joyce B Zeggini, Eleftheria Spector, Timothy D Gonzalez, Antonio |
author_facet | Rodriguez-Fontenla, Cristina Calaza, Manuel Evangelou, Evangelos Valdes, Ana M Arden, Nigel Blanco, Francisco J Carr, Andrew Chapman, Kay Deloukas, Panos Doherty, Michael Esko, Tõnu Garcés Aletá, Carlos M Gomez-Reino Carnota, Juan J Helgadottir, Hafdis Hofman, Albert Jonsdottir, Ingileif Kerkhof, Hanneke J M Kloppenburg, Margreet McCaskie, Andrew Ntzani, Evangelia E 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 Thorleifsson, Gudmar Tsezou, Aspasia Uitterlinden, André G Wallis, Gillian A Wilkinson, J Mark Zhai, Guangju Zhu, Yanyan Felson, David T Ioannidis, John P A Loughlin, John Metspalu, Andres Meulenbelt, Ingrid Stefansson, Kari van Meurs, Joyce B Zeggini, Eleftheria Spector, Timothy D Gonzalez, Antonio |
author_sort | Rodriguez-Fontenla, Cristina |
collection | PubMed |
description | OBJECTIVE: To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. METHODS: A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 × 10(−5) were considered significant. RESULTS: SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10(−5), odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06−1.17) and rs1241164 (P = 1.47 × 10(−5), OR 0.82, 95% CI 0.74−0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10(−5), OR 0.87, 95% CI 0.82−0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10(−5), OR 0.85, 95% CI 0.79−0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened. CONCLUSION: Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated. |
format | Online Article Text |
id | pubmed-4660891 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-46608912015-12-04 Assessment of Osteoarthritis Candidate Genes in a Meta-Analysis of Nine Genome-Wide Association Studies Rodriguez-Fontenla, Cristina Calaza, Manuel Evangelou, Evangelos Valdes, Ana M Arden, Nigel Blanco, Francisco J Carr, Andrew Chapman, Kay Deloukas, Panos Doherty, Michael Esko, Tõnu Garcés Aletá, Carlos M Gomez-Reino Carnota, Juan J Helgadottir, Hafdis Hofman, Albert Jonsdottir, Ingileif Kerkhof, Hanneke J M Kloppenburg, Margreet McCaskie, Andrew Ntzani, Evangelia E 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 Thorleifsson, Gudmar Tsezou, Aspasia Uitterlinden, André G Wallis, Gillian A Wilkinson, J Mark Zhai, Guangju Zhu, Yanyan Felson, David T Ioannidis, John P A Loughlin, John Metspalu, Andres Meulenbelt, Ingrid Stefansson, Kari van Meurs, Joyce B Zeggini, Eleftheria Spector, Timothy D Gonzalez, Antonio Arthritis Rheumatol Osteoarthritis OBJECTIVE: To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. METHODS: A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 × 10(−5) were considered significant. RESULTS: SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10(−5), odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06−1.17) and rs1241164 (P = 1.47 × 10(−5), OR 0.82, 95% CI 0.74−0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10(−5), OR 0.87, 95% CI 0.82−0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10(−5), OR 0.85, 95% CI 0.79−0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened. CONCLUSION: Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated. Blackwell Publishing Ltd 2014-04 2014-03-28 /pmc/articles/PMC4660891/ /pubmed/24757145 http://dx.doi.org/10.1002/art.38300 Text en © 2014 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. http://creativecommons.org/licenses/by-nc/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Osteoarthritis Rodriguez-Fontenla, Cristina Calaza, Manuel Evangelou, Evangelos Valdes, Ana M Arden, Nigel Blanco, Francisco J Carr, Andrew Chapman, Kay Deloukas, Panos Doherty, Michael Esko, Tõnu Garcés Aletá, Carlos M Gomez-Reino Carnota, Juan J Helgadottir, Hafdis Hofman, Albert Jonsdottir, Ingileif Kerkhof, Hanneke J M Kloppenburg, Margreet McCaskie, Andrew Ntzani, Evangelia E 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 Thorleifsson, Gudmar Tsezou, Aspasia Uitterlinden, André G Wallis, Gillian A Wilkinson, J Mark Zhai, Guangju Zhu, Yanyan Felson, David T Ioannidis, John P A Loughlin, John Metspalu, Andres Meulenbelt, Ingrid Stefansson, Kari van Meurs, Joyce B Zeggini, Eleftheria Spector, Timothy D Gonzalez, Antonio Assessment of Osteoarthritis Candidate Genes in a Meta-Analysis of Nine Genome-Wide Association Studies |
title | Assessment of Osteoarthritis Candidate Genes in a Meta-Analysis of Nine Genome-Wide Association Studies |
title_full | Assessment of Osteoarthritis Candidate Genes in a Meta-Analysis of Nine Genome-Wide Association Studies |
title_fullStr | Assessment of Osteoarthritis Candidate Genes in a Meta-Analysis of Nine Genome-Wide Association Studies |
title_full_unstemmed | Assessment of Osteoarthritis Candidate Genes in a Meta-Analysis of Nine Genome-Wide Association Studies |
title_short | Assessment of Osteoarthritis Candidate Genes in a Meta-Analysis of Nine Genome-Wide Association Studies |
title_sort | assessment of osteoarthritis candidate genes in a meta-analysis of nine genome-wide association studies |
topic | Osteoarthritis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660891/ https://www.ncbi.nlm.nih.gov/pubmed/24757145 http://dx.doi.org/10.1002/art.38300 |
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