To identify the susceptibility gene in hand osteoarthritis (OA) the authors used a two-stage approach genomewide 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.

dx.doi.org/10.1136/jmg.2009.067314, hdl.handle.net/1765/24903
Journal of Medical Genetics
Erasmus MC: University Medical Center Rotterdam

Zhai, G, van Meurs, J.B.J, Livshits, G, Meulenbelt, I, Valdes, A.M, Soranzo, N, … Spector, T.D. (2009). 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, 46(9), 614–616. doi:10.1136/jmg.2009.067314