Hindy G, et al. - Researchers evaluated 27,691 adults from the Malmo Diet and Cancer Study (MDCS) and 376,435 adults from the UK Biobank to study the role of cardiometabolic risk factors as a causative agent in osteoarthritis (OA) by using associated genetic variants. They calculated trait-specific polygenic risk scores for LDL- and HDL-cholesterol (LDL-C, HDL-C), triglycerides (TG), body mass index, fasting plasma glucose (FPG), and systolic blood pressure (SBP). They observed that genetically predicted raised LDL-C was linked to lower risk of OA-diagnosis and total-OA in MDCS, whereas Mendelian randomization (MR)-Egger showed pleiotropic bias and a higher correlation with OA-diagnosis, OA-joint replacement, and total-OA. They noticed no correlation among genetically predicted HDL-C, TG, FPG, or SBP, and OA consequences. They found replication of LDL-C associations in the UK Biobank, providing evidence for a causal role of lower LDL-C and higher body mass index in OA.