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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
  1. Guangju Zhai (guangju.zhai{at}kcl.ac.uk)
  1. Department of Twin Research & Genetic Epidemiology, King's College London, United Kingdom
    1. Joyce B J van Meurs (j.vanmeurs{at}erasmusmc.nl)
    1. The Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands
      1. Gregory Livshits
      1. Sackler Faculty of Medicine, Tel Aviv University, Israel
        1. Ingrid Meulenbelt
        1. Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Netherlands
          1. Ana M Valdes
          1. Department of Twin Research & Genetic Epidemiology, King's College London, United Kingdom
            1. Nicole Soranzo
            1. The Wellcome Trust Sanger Institute, United Kingdom
              1. Deborah Hart
              1. Department of Twin Research & Genetic Epidemiology, King's College London, United Kingdom
                1. Feng Zhang
                1. Department of Twin Research & Genetic Epidemiology, King's College London, United Kingdom
                  1. Bernet S Kato
                  1. Department of Twin Research & Genetic Epidemiology, King's College London, United Kingdom
                    1. Brent Richards
                    1. Department of Twin Research & Genetic Epidemiology, King's College London, United Kingdom
                      1. Frances MK Williams
                      1. Department of Twin Research & Genetic Epidemiology, King's College London, United Kingdom
                        1. Mike Inouye
                        1. The Wellcome Trust Sanger Institute, United Kingdom
                          1. Margreet Kloppenburg
                          1. Department of Rheumatology and Clinical Epidemiology, Leiden University Medical Center (LUMC), Netherlands
                            1. Panos Deloukas
                            1. The Wellcome Trust Sanger Institute, United Kingdom
                              1. Eline Slagboom
                              1. Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Netherlands
                                1. Andre Uitterlinden
                                1. The Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands
                                  1. Tim D Spector (tim.spector{at}kcl.ac.uk)
                                  1. Department of Twin Research & Genetic Epidemiology, King's College London, United Kingdom

                                    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.

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