Beyond the joint: Genetic and epidemiological insights into osteoarthritis

This thesis aims to identify risk factors for osteoarthritis, particularly the roles of physical activity and muscle mass, chondrocalcinosis, and genetics. To achieve this aim, in Chapter 2, we examined whether associations between activity type (weight-bearing vs non–weight–bearing) and incident knee osteoarthritis differed by lower-limb muscle mass. In Chapter 3.1, we studied the association between knee chondrocalcinosis and osteoarthritis by addressing the “chicken-or-egg” question, evaluating whether radiographic chondrocalcinosis preceded and was associated with incident radiographic knee OA in large, prospective cohorts. In Chapter 3.2, we investigated the genetic architecture of chondrocalcinosis through a GWAS and functional follow-up to identify susceptibility loci and the biological processes underlying chondrocalcinosis. Finally, in Chapter 4, we applied C-GWAS to large osteoarthritis datasets to identify novel osteoarthritis variants and identify multi-trait effect variants.