Background Overall, total joint replacement (TJR) of the hip or knee joint has proven to be a successful treatment of primary and secondary osteoarthritis (OA) as well as other degenerative joint diseases and fractures. Yet, a considerable portion of all patients treated with TJR are subject to revision surgery for aseptic loosening, infection or dislocation amongst other reasons (1). The risk for revision surgery of the hip or knee joint subsequent to primary arthroplasty seems to be influenced by the individuals’ genetic profile to some extent. Several candidate-driven studies have identified certain single nucleotide polymorphisms (SNP) associated with the risk for revision surgery (2–5). Most notably, both MacInnes et al. and our own research group have performed genome-wide association studies (GWAS) and found associations between SNPs and the risk for revision surgery for aseptic loosening following TJR (6,7). We now seek to replicate and thus verify the results obtained in our preliminary study. Aims and hypothesis The aim of the proposed study is to identify SNPs associated with a higher risk for revision arthroplasty subsequent to primary TJR. In particular, we aim to verify and validate the results reported in our previous study. Hence, our hypothesis is that certain SNPs increase the risk for revision arthroplasty. Methodology We plan to perform a GWAS on a subgroup of patients within the SIMPLER-cohort. All patients treated with a TJR of the hip or knee joint as indicated by the surgical procedure codes NFBXX and NGBXX will be included in the study. Data on diagnosis, age and BMI at primary TJR, along with the specific procedural code will be collected. For all patients undergoing revision arthroplasty, information on reason for revision surgery, age, BMI and procedural codes at revision surgery will be gathered. Furthermore, for all deceased patients, date of death will be checked for to enable time-to-event analysis. Lastly, the cohort will be cross-matched against the Swedish Arthroplasty Register to ensure that no secondary procedures went unnoticed. After data collection, we aim to perform a GWAS with the primary endpoint revision surgery for aseptic loosening in the above defined study population. Our secondary endpoint is revision surgery of the affected hip or knee joint for any cause.