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'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; arcOGEN Consortium; J Loughlin

doi:10.1136/ard.2010.141473

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

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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, …

Annals of the rheumatic diseases, Vol.70(5), pp.864-867

01/05/2011

DOI: https://doi.org/10.1136/ard.2010.141473

PMCID: PMC3070286

PMID: 21177295

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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Title: Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study
Creators - without role: K Panoutsopoulou - Wellcome Sanger Institute
L Southam - University of Oxford
K S Elliott - University of Oxford
N Wrayner - University of Oxford
G Zhai - King's College London
C Beazley - Wellcome Sanger Institute
G Thorleifsson - deCODE Genetics
N K Arden - University of Southampton
A Carr - University of Oxford
K Chapman - University of Oxford
P Deloukas - Wellcome Sanger Institute
M Doherty - University of Nottingham
A McCaskie - Freeman Hospital
W E R Ollier - University of Manchester
S H Ralston - University of Edinburgh
T D Spector - King's College London
A M Valdes - King's College London
G A Wallis - University of Manchester
J M Wilkinson - Northern General Hospital
E Arden - Southampton General Hospital
K Battley - INIBIC-Hospital Universitario A Coruña, Osteoarticular and Aging Research Laboratory, A Coruña, Spain
H Blackburn - Wellcome Sanger Institute
F J Blanco - INIBIC-Hospital Universitario A Coruña, Osteoarticular and Aging Research Laboratory, A Coruña, Spain
S Bumpstead - Wellcome Sanger Institute
L A Cupples - Boston University
A G Day-Williams - Wellcome Sanger Institute
K Dixon - University of Manchester
S A Doherty - University of Nottingham
T Esko - Estonian Biocenter, Tartu, Estonia
E Evangelou - University of Ioannina
D Felson - Boston University School of Medicine
J J Gomez-Reino - Universidade de Santiago de Compostela
A Gonzalez - Laboratorio de Investigacion , Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain
A Gordon - University of Sheffield
R Gwilliam - Wellcome Sanger Institute
B V Halldorsson - Reykjavic University, Reykjavik, Iceland
V B Hauksson - deCODE Genetics
A Hofman - Genomics
S E Hunt - Wellcome Sanger Institute
J P A Ioannidis - Stanford University
T Ingvarsson - University of Iceland
I Jonsdottir - University of Iceland
H Jonsson - Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland
R Keen - Royal National Orthopaedic Hospital
H J M Kerkhof - Genomics
M G Kloppenburg - Leiden University
N Koller - University of Edinburgh
N Lakenberg - Leiden University
N E Lane - Aging Center, Medicine and Rheumatology, University of California at Davis Medical Center, Sacramento, California, USA
A T Lee - Feinstein Institute for Medical Research
A Metspalu - Estonian Biocenter, Tartu, Estonia
I Meulenbelt - Leiden University
M C Nevitt - University of California, San Francisco
F O'Neill - King's College London
N Parimi - California Pacific Medical Center, San Francisco, California, USA
S C Potter - Wellcome Sanger Institute
I Rego-Perez - INIBIC-Hospital Universitario A Coruña, Osteoarticular and Aging Research Laboratory, A Coruña, Spain
J A Riancho - Universidad de Cantabria
K Sherburn - University of Manchester
P E Slagboom - Leiden University
K Stefansson - University of Iceland
U Styrkarsdottir - deCODE Genetics
M Sumillera - Marqués de Valdecilla University Hospital
D Swift - Northern General Hospital
U Thorsteinsdottir - University of Iceland
A Tsezou - University of Thessaly
A G Uitterlinden - Genomics
J B J van Meurs - Genomics
B Watkins - University of Oxford
M Wheeler - University of Nottingham
S Mitchell - Freeman Hospital
Y Zhu - Boston University School of Medicine
J M Zmuda - University of Pittsburgh
E Zeggini - University of Oxford
arcOGEN Consortium
J Loughlin - Newcastle University
Publication Details: Annals of the rheumatic diseases, Vol.70(5), pp.864-867
Identifiers: 9937249408331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article