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


ABSTRACT: 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.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.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).Novel genetic loci for hip OA were found in this meta-analysis of GWAS.

SUBMITTER: Evangelou E 

PROVIDER: S-EPMC4251181 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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

Evangelou Evangelos E   Kerkhof Hanneke J HJ   Styrkarsdottir Unnur U   Ntzani Evangelia E EE   Bos Steffan D SD   Esko Tonu T   Evans Daniel S DS   Metrustry Sarah S   Panoutsopoulou Kalliope K   Ramos Yolande F M YF   Thorleifsson Gudmar G   Tsilidis Konstantinos K KK   Arden Nigel N   Aslam Nadim N   Bellamy Nicholas N   Birrell Fraser F   Blanco Francisco J FJ   Carr Andrew A   Chapman Kay K   Day-Williams Aaron G AG   Deloukas Panos P   Doherty Michael M   Engström Gunnar G   Helgadottir Hafdis T HT   Hofman Albert A   Ingvarsson Thorvaldur T   Jonsson Helgi H   Keis Aime A   Keurentjes J Christiaan JC   Kloppenburg Margreet M   Lind Penelope A PA   McCaskie Andrew A   Martin Nicholas G NG   Milani Lili L   Montgomery Grant W GW   Nelissen Rob G H H RG   Nevitt Michael C MC   Nilsson Peter M PM   Ollier William Er WE   Parimi Neeta N   Rai Ashok A   Ralston Stuart H SH   Reed Mike R MR   Riancho Jose A JA   Rivadeneira Fernando F   Rodriguez-Fontenla Cristina C   Southam Lorraine L   Thorsteinsdottir Unnur U   Tsezou Aspasia A   Wallis Gillian A GA   Wilkinson J Mark JM   Gonzalez Antonio A   Lane Nancy E NE   Lohmander L Stefan LS   Loughlin John J   Metspalu Andres A   Uitterlinden Andre G AG   Jonsdottir Ingileif I   Stefansson Kari K   Slagboom P Eline PE   Zeggini Eleftheria E   Meulenbelt Ingrid I   Ioannidis John Pa JP   Spector Tim D TD   van Meurs Joyce B J JB   Valdes Ana M AM  

Annals of the rheumatic diseases 20130829 12


<h4>Objectives</h4>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.<h4>Methods</h4>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 stratif  ...[more]

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