title: Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study.
abstract: OBJECTIVE
  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.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
authors.forename: K
authors.initials: K
authors.lastname: Panoutsopoulou
authors.forename: L
authors.initials: L
authors.lastname: Southam
authors.forename: K S
authors.initials: KS
authors.lastname: Elliott
authors.forename: N
authors.initials: N
authors.lastname: Wrayner
authors.forename: G
authors.initials: G
authors.lastname: Zhai
authors.forename: C
authors.initials: C
authors.lastname: Beazley
authors.forename: G
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: N K
authors.initials: NK
authors.lastname: Arden
authors.forename: A
authors.initials: A
authors.lastname: Carr
authors.forename: K
authors.initials: K
authors.lastname: Chapman
authors.forename: P
authors.initials: P
authors.lastname: Deloukas
authors.forename: M
authors.initials: M
authors.lastname: Doherty
authors.forename: A
authors.initials: A
authors.lastname: McCaskie
authors.forename: W E R
authors.initials: WE
authors.lastname: Ollier
authors.forename: S H
authors.initials: SH
authors.lastname: Ralston
authors.forename: T D
authors.initials: TD
authors.lastname: Spector
authors.forename: A M
authors.initials: AM
authors.lastname: Valdes
authors.forename: G A
authors.initials: GA
authors.lastname: Wallis
authors.forename: J M
authors.initials: JM
authors.lastname: Wilkinson
authors.forename: E
authors.initials: E
authors.lastname: Arden
authors.forename: K
authors.initials: K
authors.lastname: Battley
authors.forename: H
authors.initials: H
authors.lastname: Blackburn
authors.forename: F J
authors.initials: FJ
authors.lastname: Blanco
authors.forename: S
authors.initials: S
authors.lastname: Bumpstead
authors.forename: L A
authors.initials: LA
authors.lastname: Cupples
authors.forename: A G
authors.initials: AG
authors.lastname: Day-Williams
authors.forename: K
authors.initials: K
authors.lastname: Dixon
authors.forename: S A
authors.initials: SA
authors.lastname: Doherty
authors.forename: T
authors.initials: T
authors.lastname: Esko
authors.forename: E
authors.initials: E
authors.lastname: Evangelou
authors.forename: D
authors.initials: D
authors.lastname: Felson
authors.forename: J J
authors.initials: JJ
authors.lastname: Gomez-Reino
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez
authors.forename: A
authors.initials: A
authors.lastname: Gordon
authors.forename: R
authors.initials: R
authors.lastname: Gwilliam
authors.forename: B V
authors.initials: BV
authors.lastname: Halldorsson
authors.forename: V B
authors.initials: VB
authors.lastname: Hauksson
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: S E
authors.initials: SE
authors.lastname: Hunt
authors.forename: J P A
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: T
authors.initials: T
authors.lastname: Ingvarsson
authors.forename: I
authors.initials: I
authors.lastname: Jonsdottir
authors.forename: H
authors.initials: H
authors.lastname: Jonsson
authors.forename: R
authors.initials: R
authors.lastname: Keen
authors.forename: H J M
authors.initials: HJ
authors.lastname: Kerkhof
authors.forename: M G
authors.initials: MG
authors.lastname: Kloppenburg
authors.forename: N
authors.initials: N
authors.lastname: Koller
authors.forename: N
authors.initials: N
authors.lastname: Lakenberg
authors.forename: N E
authors.initials: NE
authors.lastname: Lane
authors.forename: A T
authors.initials: AT
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Metspalu
authors.forename: I
authors.initials: I
authors.lastname: Meulenbelt
authors.forename: M C
authors.initials: MC
authors.lastname: Nevitt
authors.forename: F
authors.initials: F
authors.lastname: O'Neill
authors.forename: N
authors.initials: N
authors.lastname: Parimi
authors.forename: S C
authors.initials: SC
authors.lastname: Potter
authors.forename: I
authors.initials: I
authors.lastname: Rego-Perez
authors.forename: J A
authors.initials: JA
authors.lastname: Riancho
authors.forename: K
authors.initials: K
authors.lastname: Sherburn
authors.forename: P E
authors.initials: PE
authors.lastname: Slagboom
authors.forename: K
authors.initials: K
authors.lastname: Stefansson
authors.forename: U
authors.initials: U
authors.lastname: Styrkarsdottir
authors.forename: M
authors.initials: M
authors.lastname: Sumillera
authors.forename: D
authors.initials: D
authors.lastname: Swift
authors.forename: U
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: A
authors.initials: A
authors.lastname: Tsezou
authors.forename: A G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: J B J
authors.initials: JB
authors.lastname: van Meurs
authors.forename: B
authors.initials: B
authors.lastname: Watkins
authors.forename: M
authors.initials: M
authors.lastname: Wheeler
authors.forename: S
authors.initials: S
authors.lastname: Mitchell
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: J M
authors.initials: JM
authors.lastname: Zmuda
authors.forename: E
authors.initials: E
authors.lastname: Zeggini
authors.forename: J
authors.initials: J
authors.lastname: Loughlin
mesh_terms: D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020412:Multifactorial Inheritance; D015207:Osteoarthritis, Hip / Q000235:genetics*; D020370:Osteoarthritis, Knee / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide