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

Guangju Zhai (1) , Joyce B J van Meurs (2) , Gregory Livshits (3) , Ingrid Meulenbelt (4) , Ana M Valdes (1) , Nicole Soranzo (5) , Deborah Hart (1) , Feng Zhang (1) , Bernet S Kato (1) , Brent Richards (1) , Frances Mk Williams (1) , Mike Inouye (5) , Margreet Kloppenburg (6) , Panos Deloukas (5) , Eline Slagboom (4) , Andre Uitterlinden (2) , Tim D Spector (1)

1 King‘s College London
2 Erasmus MC - Erasmus University Medical Center [Rotterdam]
3 TAU - Tel Aviv University
4 Section Molecular Epidemiology, Leiden University Medical Center (LUMC)
5 The Wellcome Trust Sanger Institute [Cambridge]
6 Department of Rheumatology and Clinical Epidemiology, Leiden University Medical Center (LUMC)

To identify hand OA susceptibility gene, we utilized a two-stage approach genome-wide association study (GWAS) using two discovery samples (the TwinsUK cohort and the Rotterdam discovery subset; a total of 1804 individuals) and four replication samples (the Chingford study, the Chuvasha Skeletal Aging study, the Rotterdam replication subset, and the GARP Study; a total of 3266 individuals). 5 SNPs suggested the 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 33-41% using a case-control definition. The SNP is located in intron 1 of the A2BP1 gene. We 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. Our findings provide a potential new insight into genetic mechanisms in the development of hand OA.

Mots clés: Osteoarthritis; Genetic epidemiology

Guangju Zhai, Joyce B J van Meurs, Gregory Livshits, Ingrid Meulenbelt, Ana M Valdes, et al.. 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. Journal of Medical Genetics, 2009, 46 (9), pp.614. ⟨10.1136/jmg.2009.067314⟩. ⟨hal-00552696⟩