biostudies-literatureYu Hthe Science and Technology Program of Xi'an, Shaanxi ProvincePostdoctoral Fund of Shaanxi Provincethe Science and Technology Program of Xi&apos;an, Shaanxi Province119https://www.ebi.ac.uk/biostudies/studies/S-EPMC11976339biostudies-literatureUnknown37(1)<h4>Background</h4>Despite well-documented associations between Body mass index (BMI) and Osteoarthritis (OA), the specific biological pathways and mediators involved remain poorly understood. This study aims to explore mediators through which BMI influences OA risk, particularly knee osteoarthritis (KOA), using Mendelian Randomization (MR) and mediation analysis.<h4>Methods</h4>We used a two-step MR approach with data from the IEU OpenGWAS and FinnGen version 7 databases. BMI (N = 322,154) was the primary exposure, with knee disorders (KD), total bone mineral density (TBMD), metabolic disorders (MD), and anxiety disorders (AD) as potential mediators. Outcomes included KOA (N = 22,347), hip OA (HOA) (N = 11,989), and all OA (AllOA) (N = 50,508). Univariate MR evaluated causal relationshipsAging clinical and experimental researchRevealing the mediating mechanisms between BMI and osteoarthritis: a Mendelian randomization and mediation analysis.PMC119763392023BSHGZZHQYXMZZ0224YXYJ0085Li HGuo JXu XWang JYu HfalseRevealing the mediating mechanisms between BMI and osteoarthritis: a Mendelian randomization and mediation analysis.<h4>Background</h4>Despite well-documented associations between Body mass index (BMI) and Osteoarthritis (OA), the specific biological pathways and mediators involved remain poorly understood. This study aims to explore mediators through which BMI influences OA risk, particularly knee osteoarthritis (KOA), using Mendelian Randomization (MR) and mediation analysis.<h4>Methods</h4>We used a two-step MR approach with data from the IEU OpenGWAS and FinnGen version 7 databases. BMI (N = 322,154) was the primary exposure, with knee disorders (KD), total bone mineral density (TBMD), metabolic disorders (MD), and anxiety disorders (AD) as potential mediators. Outcomes included KOA (N = 22,347), hip OA (HOA) (N = 11,989), and all OA (AllOA) (N = 50,508). Univariate MR evaluated causal relationships2025-01-01T00:00:00Z2025 Apr2026-07-15T05:01:17.099Z2025-07-12T03:04:18.307ZS-EPMC119763394019290210.1007/s40520-025-03035-2