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Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study.

Panoutsopoulou, K; Southam, L; Elliott, K S; Wrayner, N; Zhai, G; Beazley, C; Thorleifsson, G; Arden, N K; Carr, A; Chapman, K; Deloukas, P; Doherty, M; McCaskie, A; Ollier, W E R; Ralston, S H; Spector, T D; Valdes, A M; Wallis, G A; Wilkinson, J M; Arden, E; Battley, K; Blackburn, H; Blanco, F J; Bumpstead, S; Cupples, L A; Day-Williams, A G; Dixon, K; Doherty, S A; Esko, T; Evangelou, E; Felson, D; Gomez-Reino, J J; Gonzalez, A; Gordon, A; Gwilliam, R; Halldorsson, B V; Hauksson, V B; Hofman, A; Hunt, S E; Ioannidis, J P A; Ingvarsson, T; Jonsdottir, I; Jonsson, H; Keen, R; Kerkhof, H J M; Kloppenburg, M G; Koller, N; Lakenberg, N; Lane, N E; Lee, A T; Metspalu, A; Meulenbelt, I; Nevitt, M C; O'Neill, F; Parimi, N; Potter, S C; Rego-Perez, I; Riancho, J A; Sherburn, K; Slagboom, P E; Stefansson, K; Styrkarsdottir, U; Sumillera, M; Swift, D; Thorsteinsdottir, U; Tsezou, A; Uitterlinden, A G; van Meurs, J B J; Watkins, B; Wheeler, M; Mitchell, S; Zhu, Y; Zmuda, J M; arcOGEN consortium; Zeggini, E; Loughlin, J

Annals of the rheumatic diseases. 2011;70(5):864-7.

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Abstract

OBJECTIVES: The genetic aetiology of osteoarthritis has not yet been elucidated. To enable a well-powered genome-wide association study (GWAS) for osteoarthritis, the authors have formed the arcOGEN Consortium, a UK-wide collaborative effort aiming to scan genome-wide over 7500 osteoarthritis cases in a two-stage genome-wide association scan. Here the authors report the findings of the stage 1 interim analysis. METHODS: The authors have performed a genome-wide association scan for knee and hip osteoarthritis in 3177 cases and 4894 population-based controls from the UK. Replication of promising signals was carried out in silico in five further scans (44,449 individuals), and de novo in 14 534 independent samples, all of European descent. RESULTS: None of the association signals the authors identified reach genome-wide levels of statistical significance, therefore stressing the need for corroboration in sample sets of a larger size. Application of analytical approaches to examine the allelic architecture of disease to the stage 1 genome-wide association scan data suggests that osteoarthritis is a highly polygenic disease with multiple risk variants conferring small effects. CONCLUSIONS: Identifying loci conferring susceptibility to osteoarthritis will require large-scale sample sizes and well-defined phenotypes to minimise heterogeneity.

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Published date:
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Place of publication:
England
Volume:
70
Issue:
5
Pagination:
864-7
Digital Object Identifier:
10.1136/ard.2010.141473
Pubmed Identifier:
21177295
Pii Identifier:
ard.2010.141473
Access state:
Active

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Record metadata

Manchester eScholar ID:
uk-ac-man-scw:125776
Created by:
Hookway, Sue
Created:
1st July, 2011, 07:39:53
Last modified by:
Hookway, Sue
Last modified:
20th July, 2015, 12:55:49

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