Aug 31, 2013

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

Annals of the Rheumatic Diseases
Evangelos EvangelouAna M Valdes

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...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
IFRD1 protein, human
Meta-Analysis (Publications)
Immediate-Early Proteins
Degenerative Polyarthritis
HMGN Proteins
NCOA3 gene
Structure of Articular Cartilage
Entire Articular Cartilage
European Continental Ancestry Group

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