The causal relationship between emotions and osteoarthritis: A bidirectional Mendelian randomization study

Previous study has observed the clinical relationship between affective disorders such as depression and anxiety and osteoarthritis (OA), however the gene causal effect was still unclear. The objective of this study was to evaluate the genetic causal effect of emotions on OA using bidirectional Mendelian randomization (MR), which is a novel methodology elucidating the causal relationship between diseases and screening for the potential driver genes. A bidirectional MR study was conducted to assess the causal effect of emotion on OA. The instrumental variables were selected from publicly available Genome-Wide Association Study summary datasets based on a P-value threshold (P < 5e-8) and linkage disequilibrium clumping criteria (r² < 0.001, window size = 10,000 kb). The robustness of the findings across different MR methods was validated by Cochran Q test, MR-Egger intercept test, MR_PRESSO, F-statistic, and statistical power. The inverse-variance weighted method was employed as the primary analysis due to its weighting approach, which minimizes variance and yields the most precise estimation of causal effects. While MR-Egger (assessed and accounted Pleiotropy), Weighted Median (adjusted for the potential confounding pleiotropy of instrumental variables), Weighted and Simple Mode (identified the effect clusters) methods were used as supplementary analyses to complement the outcome. The main genetic data source consisted of 10,083 participants obtained from publicly accessible repository. The emotions of depression, anxiousness, and hurt were found to have a genetic influence on the development of OA. Specifically, anxiousness was associated with a reduced risk of OA (odds ratio [OR] = 0.486, 95% confidence interval [CI] = 0.260-0.908, P = .024). On the other hand, depression (OR = 2.157, 95% CI = 1.605-2.899, P = 3.4e-07) and hurt (OR = 1.731, 95% CI = 1.092-2.745, P = .020) were identified as genetic factors that increased the susceptibility to OA. The statistical power of depression, anxious and feeling hurt on OA were > 0.99, 0.29, and > 0.99. These findings suggest that genetic factors underlying emotions, particularly depression and emotional distress, significantly influence susceptibility to OA, underscoring the potential for targeted mental health interventions in OA management.