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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2130-2136 |
| Number of pages | 7 |
| Journal | Annals of the Rheumatic Diseases |
| Volume | 73 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2014 |
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Keywords
- Epidemiology
- Gene Polymorphism
- Osteoarthritis
ASJC Scopus subject areas
- Immunology and Allergy
- Rheumatology
- Immunology
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip. / arcOGEN Consortium.
In: Annals of the Rheumatic Diseases, Vol. 73, No. 12, 01.12.2014, p. 2130-2136.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
AU - arcOGEN Consortium
AU - Evangelou, Evangelos
AU - Kerkhof, Hanneke J.
AU - Styrkarsdottir, Unnur
AU - Ntzani, Evangelia E.
AU - Bos, Steffan D.
AU - Esko, Tonu
AU - Evans, Daniel S.
AU - Metrustry, Sarah
AU - Panoutsopoulou, Kalliope
AU - Ramos, Yolande F.M.
AU - Thorleifsson, Gudmar
AU - Tsilidis, Konstantinos K.
AU - Arden, Nigel
AU - Aslam, Nadim
AU - Bellamy, Nicholas
AU - Birrell, Fraser
AU - Blanco, Francisco J.
AU - Carr, Andrew
AU - Chapman, Kay
AU - Day-Williams, Aaron G.
AU - Deloukas, Panos
AU - Doherty, Michael
AU - Engström, Gunnar
AU - Helgadottir, Hafdis T.
AU - Hofman, Albert
AU - Ingvarsson, Thorvaldur
AU - Jonsson, Helgi
AU - Keis, Aime
AU - Keurentjes, J. Christiaan
AU - Kloppenburg, Margreet
AU - Lind, Penelope A.
AU - McCaskie, Andrew
AU - Martin, Nicholas G.
AU - Milani, Lili
AU - Montgomery, Grant W.
AU - Nelissen, Rob G.H.H.
AU - Nevitt, Michael C.
AU - Nilsson, Peter M.
AU - Ollier, William E.R.
AU - Parimi, Neeta
AU - Rai, Ashok
AU - Ralston, Stuart H.
AU - Reed, Mike R.
AU - Riancho, Jose A.
AU - Rivadeneira, Fernando
AU - Rodriguez-Fontenla, Cristina
AU - Southam, Lorraine
AU - Thorsteinsdottir, Unnur
AU - Tsezou, Aspasia
AU - Lane, Nancy E
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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.
KW - Epidemiology
KW - Gene Polymorphism
KW - Osteoarthritis
UR - http://www.scopus.com/inward/record.url?scp=85003346464&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85003346464&partnerID=8YFLogxK
U2 - 10.1136/annrheumdis-2012-203114
DO - 10.1136/annrheumdis-2012-203114
M3 - Article
C2 - 23989986
AN - SCOPUS:84883445177
VL - 73
SP - 2130
EP - 2136
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
SN - 0003-4967
IS - 12
ER -