Abstract
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.