Type 2 Diabetes and Glycemic Traits Are Not Causal Factors of Osteoarthritis: A Two-Sample Mendelian Randomization Analysis

It remains unclear whether an increased risk of type 2 diabetes (T2D) affects the risk of osteoarthritis (OA). Here, we used two-sample Mendelian randomization (MR) to obtain non-confounded estimates of the effect of T2D and glycemic traits on hip and knee OA. We identified single-nucleotide polymorphisms (SNPs) strongly associated with T2D, fasting glucose (FG), and 2-h postprandial glucose (2hGlu) from genome-wide association studies (GWAS). We used the MR inverse variance weighted (IVW), the MR-Egger method, the weighted median (WM), and the Robust Adjusted Profile Score (MR.RAPS) to reveal the associations of T2D, FG, and 2hGlu with hip and knee OA risks. Sensitivity analyses were also conducted to verify whether heterogeneity and pleiotropy can bias the MR results. We did not find statistically significant causal effects of genetically increased T2D risk, FG, and 2hGlu on hip and knee OA (e.g., T2D and hip OA, MR-Egger OR = 1.1708, 95% CI 0.9469-1.4476, = 0.1547). It was confirmed that horizontal pleiotropy was unlikely to bias the causality (e.g., T2D and hip OA, MR-Egger, intercept = -0.0105, = 0.1367). No evidence of heterogeneity was found between the genetic variants (e.g., T2D and hip OA, MR-Egger = 30.1362, < 0.0001, = 0.6104). Our MR study did not support causal effects of a genetically increased T2D risk, FG, and 2hGlu on hip and knee OA risk.