Recent genome wide association studies have revealed several osteoarthritis (OA) risk loci involve common genetic variations related to musculoskeletal development and morphogenesis. To date, a major shortcoming in this virginal research area, however, is that morphometric phenotyping is based on 2D superposition imaging resulting in high noise levels and lacking applicability. In this interdisciplinary project, DNA will be collected from patients undergoing a high-resolution CT scan for medical purposes. To establish the role of shape and biomechanical variance as an independent risk factor in OA , our project provides the opportunity to explore the joint geometry and mechanical phenotype at a population wide level. Next, subject-specific contact stresses can be computed by means of a validated discrete element analysis approach. For each configuration, the genetic constitution will be found, and corresponding mechanical phenotypes can be explored. Findings will be benchmarked by identification of high-load bearing zones in patients having end-stage OA using a large validation cohort of +1200 OA cases