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J Med Genet 2009;46:614-616 doi:10.1136/jmg.2009.067314
  • Short report

A genome-wide association study suggests that a locus within the ataxin 2 binding protein 1 gene is associated with hand osteoarthritis: the Treat-OA consortium

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  1. G Zhai1,
  2. J B J van Meurs2,
  3. G Livshits3,
  4. I Meulenbelt4,
  5. A M Valdes1,
  6. N Soranzo5,1,
  7. D Hart1,
  8. F Zhang1,
  9. B S Kato1,
  10. J B Richards1,
  11. F M K Williams1,
  12. M Inouye5,
  13. M Kloppenburg6,
  14. P Deloukas5,
  15. E Slagboom4,
  16. A Uitterlinden2,
  17. T D Spector1
  1. 1
    Department of Twin Research & Genetic Epidemiology, King’s College London, UK
  2. 2
    The Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands
  3. 3
    Sackler Faculty of Medicine, Tel Aviv University, Israel
  4. 4
    Section Molecular Epidemiology, Leiden University Medical Center (LUMC), the Netherlands
  5. 5
    The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK
  6. 6
    Department of Rheumatology and Clinical Epidemiology, Leiden University Medical Center (LUMC), the Netherlands
  1. Correspondence to Dr G Zhai, Department of Twin Research & Genetic Epidemiology, King’s College London, UK; guangju.zhai{at}kcl.ac.uk
  • Received 19 February 2009
  • Revised 3 April 2009
  • Accepted 21 April 2009
  • Published Online First 8 June 2009

Abstract

To identify the susceptibility gene in hand osteoarthritis (OA) the authors used a two-stage approach genome-wide association study using two discovery samples (the TwinsUK cohort and the Rotterdam discovery subset; a total of 1804 subjects) and four replication samples (the Chingford Study, the Chuvasha Skeletal Aging Study, the Rotterdam replication subset and the Genetics, Arthrosis, and Progression (GARP) Study; a total of 3266 people). Five single-nucleotide polymorphisms (SNPs) had a likelihood of association with hand OA in the discovery stage and one of them (rs716508), was successfully confirmed in the replication stage (meta-analysis p = 1.81×10−5). The C allele conferred a reduced risk of 33% to 41% using a case–control definition. The SNP is located in intron 1 of the A2BP1 gene. This study also found that the same allele of the SNP significantly reduced bone density at both the hip and spine (p<0.01), suggesting the potential mechanism of the gene in hand OA might be via effects on subchondral bone. The authors' findings provide a potential new insight into genetic mechanisms in the development of hand OA.

Footnotes

  • ‣ Additional data are published online only at http://jmg.bmj.com/content/vol46/issue9

  • Funding European Community Framework 7 large collaborative project grant Treat-OA, The Wellcome Trust; Arthritis Research Campaign, The study also receives support from the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London. TDS is an NIHR senior Investigator. The project also received support from a Biotechnology and biological Sciences Research Council (BBSRC) project grant and NHS National Institute for Health Research (TS).

  • Competing interests None.

  • Ethics approval St Thomas' Hospital Research Ethics Committee approved the study.

  • Provenance and Peer review Not commissioned; externally peer reviewed.

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