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

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Authors
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
Zeggini, E
Loughlin, J
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Issue Date
2011-05

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Citation
Ann. Rheum. Dis. 2011, 70(5):864-7
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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Additional Links
http://dx.doi.org/10.1136/ard.2010.141473
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070286/?tool=pubmed
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Archived with thanks to Annals of the rheumatic diseases
ae974a485f413a2113503eed53cd6c53
10.1136/ard.2010.141473
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