Association and Bidirectional Causal Relationship Between Depression and Osteoarthritis: Evidence From NHANES and Mendelian Randomization

ABSTRACT Background Depression is significant among patients with arthritis and musculoskeletal illnesses. However, while the impact of osteoarthritis (OA) on depression has been extensively studied, the reverse—whether depression leads to osteoarthritis—has not been widely explored. The purpose of this study is to investigate the correlation and causal relationship between depression and OA. Methods Firstly, the National Health and Nutrition Examination Survey (NHANES) database was used to construct a logistic regression model to explore the correlation between depression and OA. The odds ratio (OR) with corresponding 95% confidence interval (CI) was employed to evaluate the results. Subgroup analysis and sensitivity analysis were also done to verify the stability of the results. Then, Mendelian randomization (MR) was used to explore the bidirectional causal relationship between depression and OA. The inverse‐variance weighted (IVW) method was used as the primary analytical method to assess causality. In addition, other MR methods (Egger intercept, leave‐one‐out, and MR‐Egger) were performed to assess heterogeneity, horizontal and pleiotropy. Results Multivariate logistic regression results showed that depression and OA were positively correlated (OR = 2.33(1.87–2.9), p < 0.001). Subgroup analyses and sensitivity analyses further demonstrated the robustness of the results. MR showed a bidirectional causal relationship between depression and OA (all OR values > 1, p < 0.05). Additionally, no horizontal pleiotropy or heterogeneity was observed. Meta‐analysis results further indicated a bidirectional relationship between depression and OA. Conclusion Depression and OA have a correlation and bidirectional causal relationship on multiple levels.