Ann Rheum Dis 70:864-867 doi:10.1136/ard.2010.141473
  • Basic and translational research
  • Concise report

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

Open Access
  1. J Loughlin10
  1. 1Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK
  2. 2Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
  3. 3Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
  4. 4Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
  5. 5Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
  6. 6deCODE Genetics, Reykjavik, Iceland
  7. 7NIHR Biomedical Research Unit, University of Oxford, Oxford, UK
  8. 8MRC Epidemiology Resource Centre, University of Southampton, Southampton, UK
  9. 9Academic Rheumatology, University of Nottingham, Nottingham, UK
  10. 10Institute of Cellular Medicine, Musculoskeletal Research Group, Newcastle University, Newcastle upon Tyne, UK
  11. 11The Newcastle upon Tyne Hospitals NHS Trust Foundation Trust, The Freeman Hospital, Byker, Newcastle upon Tyne, UK
  12. 12Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK
  13. 13Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  14. 14Wellcome Trust Centre for Cell Matrix Research, University of Manchester, Manchester, UK
  15. 15Academic Unit of Bone Metabolism, Department of Human Metabolism, University of Sheffield, Sheffield, UK
  16. 16Sheffield NIHR Bone Biomedical Research Unit, Centre for Biomedical Research, Northern General Hospital, Sheffield, UK
  17. 17Wellcome Trust Clinical Research Facility, Southampton General Hospital, Southampton, UK
  18. 18INIBIC-Hospital Universitario A Coruña, Osteoarticular and Aging Research Laboratory, A Coruña, Spain
  19. 19Boston University School of Public Health, Boston, Massachusetts, USA
  20. 20Estonian Genome Center, University of Tartu, Tartu, Estonia
  21. 21Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
  22. 22Estonian Biocenter, Tartu, Estonia
  23. 23Department of Hygiene and Epidemiology, University of Ioannina, Ioannina, Greece
  24. 24Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts, USA
  25. 25Rheumatology Unit, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain
  26. 26Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain
  27. 27Laboratorio de Investigacion 10, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain
  28. 28Reykjavic University, Reykjavik, Iceland
  29. 29Erasmus Medical Centre, Rotterdam, The Netherlands
  30. 30The Netherlands Genomics Initiative-Sponsored Netherlands Consortium for Healthy Aging, Rotterdam and Leiden, The Netherlands
  31. 31Tufts Clinical and Translational Science Institute and Tufts University School of Medicine, Boston, Massachusetts, USA
  32. 32Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
  33. 33Stanford Prevention Research Center, Stanford University, Stanford, California, USA
  34. 34Department of Health Sciences, University of Akureyri, Norðurslóð, Akureyri, Iceland
  35. 35Department of Medicine, University of Iceland, Reykjavik, Iceland
  36. 36Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland
  37. 37Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, UK
  38. 38Departments of Rheumatology and Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands
  39. 39Section of Molecular Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands
  40. 40Aging Center, Medicine and Rheumatology, University of California at Davis Medical Center, Sacramento, California, USA
  41. 41The Robert S Boas Center for Genomics and Human Genetics, The Feinstein Institute for Medical Research, Manhasset, New York, USA
  42. 42Department of Epidemiology and Biostatistics, San Francisco Coordinating Center, University of California, San Francisco, California, USA
  43. 43California Pacific Medical Center, San Francisco, California, USA
  44. 44Department of Internal Medicine, Hospital U M Valdecilla, University of Cantabria, Santander, Spain
  45. 45Department of Orthopedic Surgery and Traumatology, Hospital U M Valdecilla, Santander, Spain
  46. 46University of Thessaly, Larissa, Greece
  47. 47Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  1. Correspondence to Dr J Loughlin, Newcastle University, Institute of Cellular Medicine, 4th Floor Catherine Cookson Building, Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK; john.loughlin{at} and E Zeggini, Wellcome Trust Sanger Institute, The Morgan Building, Wellcome Trust Genome Campus, Cambridge CB10 1HH, UK, eleftheria{at}
  • Accepted 11 November 2010
  • Published Online First 21 December 2010


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.


  • KP and LS contributed equally. E Zeggini and J Loughlin contributed equally to the study.

  • Funding This study was financially supported by Arthritis Research UK.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Oxfordshire Research Ethics Committee C reference 07/H0606/150.

  • Provenance and peer review Not commissioned; externally peer reviewed

This paper is freely available online under the BMJ Journals unlocked scheme, see