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

K. Panoutsopoulou; L. Southam; K. S. Elliott; N. Wrayner; G. Zhai; C. Beazley; G. Thorleifsson; N. K. Arden; A. Carr; K. Chapman; P. Deloukas; M. Doherty; A. McCaskie; W. E. R. Ollier; S. H. Ralston; T. D. Spector; A. M. Valdes; G. A. Wallis; J. M. Wilkinson; E. Arden; K. Battley; H. Blackburn; F. J. Blanco; S. Bumpstead; L. A. Cupples; A. G. Day-Williams; K. Dixon; S. A. Doherty; T. Esko; E. Evangelou; D. Felson; J. J. Gomez-Reino; A. Gonzalez; A. Gordon; R. Gwilliam; B. V. Halldorsson; V. B. Hauksson; A. Hofman; S. E. Hunt; J. P. A. Ioannidis; T. Ingvarsson; I. Jonsdottir; H. Jonsson; R. Keen; H. J. M. Kerkhof; M. G. Kloppenburg; N. Koller; N. Lakenberg; N. E. Lane; A. T. Lee; A. Metspalu; I. Meulenbelt; M. C. Nevitt; F. O&apos;Neill; N. Parimi; S. C. Potter; I. Rego-Perez; J. A. Riancho; K. Sherburn; P. E. Slagboom; K. Stefansson; U. Styrkarsdottir; M. Sumillera; D. Swift; U. Thorsteinsdottir; A. Tsezou; A. G. Uitterlinden; J. B. J. van Meurs; B. Watkins; M. Wheeler; S. Mitchell; Y. Zhu; J. M. Zmuda; E. Zeggini; J. Loughlin

doi:10.1136/ard.2010.141473

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

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

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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.

Original language	English
Pages (from-to)	864 - 867
Number of pages	4
Journal	Annals of the Rheumatic Diseases
Volume	70
Issue number	5
DOIs	https://doi.org/10.1136/ard.2010.141473
Publication status	Published - May 2011

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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., ... Loughlin, J. (2011). Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study. Annals of the Rheumatic Diseases, 70(5), 864 - 867. https://doi.org/10.1136/ard.2010.141473

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title = "Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study",

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.",

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

year = "2011",

month = may,

doi = "10.1136/ard.2010.141473",

language = "English",

volume = "70",

pages = "864 -- 867",

journal = "Annals of the Rheumatic Diseases",

issn = "1468-2060",

publisher = "BMJ Publishing Group",

number = "5",

}

Panoutsopoulou, K, Southam, L, Elliott, KS, Wrayner, N, Zhai, G, Beazley, C, Thorleifsson, G, Arden, NK, Carr, A, Chapman, K, Deloukas, P, Doherty, M, McCaskie, A, Ollier, WER, Ralston, SH, Spector, TD , Valdes, AM, Wallis, GA, Wilkinson, JM, Arden, E, Battley, K, Blackburn, H, Blanco, FJ, Bumpstead, S, Cupples, LA, Day-Williams, AG, Dixon, K, Doherty, SA, Esko, T, Evangelou, E, Felson, D, Gomez-Reino, JJ, Gonzalez, A, Gordon, A, Gwilliam, R, Halldorsson, BV, Hauksson, VB, Hofman, A, Hunt, SE, Ioannidis, JPA, Ingvarsson, T, Jonsdottir, I, Jonsson, H, Keen, R, Kerkhof, HJM, Kloppenburg, MG, Koller, N, Lakenberg, N, Lane, NE, Lee, AT, Metspalu, A, Meulenbelt, I, Nevitt, MC, O'Neill, F, Parimi, N, Potter, SC, Rego-Perez, I, Riancho, JA, Sherburn, K, Slagboom, PE, Stefansson, K, Styrkarsdottir, U, Sumillera, M, Swift, D, Thorsteinsdottir, U, Tsezou, A, Uitterlinden, AG, van Meurs, JBJ, Watkins, B, Wheeler, M, Mitchell, S, Zhu, Y, Zmuda, JM, Zeggini, E & Loughlin, J 2011, 'Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study', Annals of the Rheumatic Diseases, vol. 70, no. 5, pp. 864 - 867. https://doi.org/10.1136/ard.2010.141473

TY - JOUR

T1 - Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study

AU - Panoutsopoulou, K.

AU - Southam, L.

AU - Elliott, K. S.

AU - Wrayner, N.

AU - Zhai, G.

AU - Beazley, C.

AU - Thorleifsson, G.

AU - Arden, N. K.

AU - Carr, A.

AU - Chapman, K.

AU - Deloukas, P.

AU - Doherty, M.

AU - McCaskie, A.

AU - Ollier, W. E. R.

AU - Ralston, S. H.

AU - Spector, T. D.

AU - Valdes, A. M.

AU - Wallis, G. A.

AU - Wilkinson, J. M.

AU - Arden, E.

AU - Battley, K.

AU - Blackburn, H.

AU - Blanco, F. J.

AU - Bumpstead, S.

AU - Cupples, L. A.

AU - Day-Williams, A. G.

AU - Dixon, K.

AU - Doherty, S. A.

AU - Esko, T.

AU - Evangelou, E.

AU - Felson, D.

AU - Gomez-Reino, J. J.

AU - Gonzalez, A.

AU - Gordon, A.

AU - Gwilliam, R.

AU - Halldorsson, B. V.

AU - Hauksson, V. B.

AU - Hofman, A.

AU - Hunt, S. E.

AU - Ioannidis, J. P. A.

AU - Ingvarsson, T.

AU - Jonsdottir, I.

AU - Jonsson, H.

AU - Keen, R.

AU - Kerkhof, H. J. M.

AU - Kloppenburg, M. G.

AU - Koller, N.

AU - Lakenberg, N.

AU - Lane, N. E.

AU - Lee, A. T.

AU - Metspalu, A.

AU - Meulenbelt, I.

AU - Nevitt, M. C.

AU - O'Neill, F.

AU - Parimi, N.

AU - Potter, S. C.

AU - Rego-Perez, I.

AU - Riancho, J. A.

AU - Sherburn, K.

AU - Slagboom, P. E.

AU - Stefansson, K.

AU - Styrkarsdottir, U.

AU - Sumillera, M.

AU - Swift, D.

AU - Thorsteinsdottir, U.

AU - Tsezou, A.

AU - Uitterlinden, A. G.

AU - van Meurs, J. B. J.

AU - Watkins, B.

AU - Wheeler, M.

AU - Mitchell, S.

AU - Zhu, Y.

AU - Zmuda, J. M.

AU - Zeggini, E.

AU - Loughlin, J.

PY - 2011/5

Y1 - 2011/5

N2 - 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.

AB - 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.

U2 - 10.1136/ard.2010.141473

DO - 10.1136/ard.2010.141473

M3 - Article

SN - 1468-2060

VL - 70

SP - 864

EP - 867

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 5

ER -

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

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