Cognitive function and knee osteoarthritis: A bidirectional Mendelian randomization study with BMI mediation

作者：Yu Zhang, Qiuxiang Lin, Debiao Yu, Tianxiang Lu, Xiaoting Chen, Y Y Lin, Jiawei Qin, Fu‐Chun Wu · 发表于：Medicine · 年份：2026 · DOI：10.1097/md.0000000000049914 · 研究领域：Osteoarthritis Treatment and Mechanisms、Genetic Associations and Epidemiology、Rheumatoid Arthritis Research and Therapies

This study investigated the causal relationship between cognitive function and knee osteoarthritis (KOA) and whether body mass index (BMI) mediates this effect. A bidirectional Mendelian randomization (MR) analysis was conducted using genome-wide association study summary statistics. The primary analysis used the inverse-variance weighted method, with MR-Egger, weighted median, robust adjusted profile score, and MR-PRESSO applied for sensitivity analyses. Forward MR analyses showed a significant inverse causal effect of cognitive function on KOA risk, with intelligence (OR = 0.843, 95% CI: 0.755-0.941, P = .002) and cognitive performance (OR = 0.850, 95% CI: 0.771-0.937, P = .001) associated with reduced risk. Reverse MR analyses found no evidence that KOA causally affects cognitive function (Intelligence: β = -0.020, 95% CI:-0.048 to 0.008, P = .167; Cognitive performance: β = -0.006, 95% CI:-0.032-0.020, P = .661). Mediation analysis showed that BMI partially mediated the effect of intelligence on KOA (indirect β = -0.047, 95% CI:-0.110 to-0.006, P = .023), accounting for 27.29% of the total effect. In conclusion, these findings support a unidirectional causal effect of cognitive function on KOA, partially mediated by BMI, highlighting the relevance of cognitive function and weight management in high-risk individuals.