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