A clinical study based on bidirectional Mendelian randomization: Correlation between generalized anxiety disorder and weight-bearing joints osteoarthritis

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ObjectivesBidirectional Mendelian randomization (MR) combined with clinical case analysis was used to elucidate the relationship between generalized anxiety disorder (GAD) caused by mental overload and the risk of weight-bearing joint (hip/knee) osteoarthritis (OA). MethodsWe performed MR analyses using publicly released genome-wide association study summary statistics to measure the causal effects between mental overload and weight-bearing joint OA risk. The primary MR analysis utilized the inverse-variance weighted (IVW) method, complemented by additional methods, including simple mode, weighted mode, MR-Egger regression, and weighted median. The leave-one-out method was used for sensitivity analysis. Concurrently, data from patients with OA (Kellgren–Lawrence grades III–IV) who needed total knee/hip arthroplasty were collected. Patient assessments were conducted utilizing the Western Ontario and McMaster Universities arthritis index, Penn State worry questionnaire, and visual analogue scale. ResultsGenetically predisposed GAD did not correlate with the risk of weight-bearing joint OA (IVW odds ratio [OR] = 0.840, 95 % confidence interval = 0.128, 5.50, P = 0.855). In reverse MR analyses, we detected no causal effect of weight-bearing OA on GAD (IVW OR = 1.00, 95 % CI = 0.985, 1.03, P = 0.687). In the clinical case evaluation, weight overload joint OA and GAD were highly correlated. ConclusionMR analysis indicated no bidirectional causal effect of GAD caused by mental overload on weight-bearing joint (hip or knee) OA. Clinical studies support the finding that GAD is highly correlated with weight-bearing joint OA. However, whether there is a causal relationship between GAD caused by mental overload and weight-overloading joint OA requires further investigation.