Hindy G, et al. - A total of 27,691 adults from the Malmo Diet and Cancer Study (MDCS) and replicated novel findings among 376,435 adults from the UK Biobank were studied to quantify the causal role of cardiometabolic risk factors in osteoarthritis (OA) using related genetic variants. An association of genetically predicted increase in low-density lipoprotein (LDL) cholesterol level with a lower risk of OA diagnosis and total OA was reported in the MDCS, supported by multivariable Mendelian randomization (MR) for OA diagnosis and total OA and by conventional 2-sample MR for OA diagnosis. They noted a correlation of genetically predicted increase in body mass index with an increased risk of OA diagnosis, while MR-Egger showed pleiotropic bias and a larger relation with OA diagnosis, OA joint replacement, and total OA. They did not find any relation between genetically predicted high-density lipoprotein cholesterol level, triglyceride level, fasting plasma glucose level, or systolic blood pressure and OA outcomes. Lower LDL and higher BMI seem to have a casual role in OA.