Jul 6, 2012

Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study

Lancet
arcOGEN consortiumJohn Loughlin

Abstract

Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. We identified five genome-wide significant loci (binomial test p≤5·0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a mi...Continue Reading

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  • Citations153

Mentioned in this Paper

Genome-Wide Association Study
Pathogenic Aspects
Biochemical Pathway
Meta-Analysis (Publications)
Exertion
Pathogenesis
Degenerative Polyarthritis
Exons
Fto Gene (Procedure)
RUNX2 gene

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