A clinical study based on bidirectional Mendelian randomization: Correlation between generalized anxiety disorder and
Xiao Ma1,2, Han Zhang1,2, Guangyu Li3
1Department of Orthopaedics, The Affiliated Hospital of Qingdao University, Qingdao, China.
Objectives:
Bidirectional 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).
Methods:
We 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.
Results:
Genetically 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.
Conclusion:
MR 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.
Insights
Mendelian randomization found no causal link between generalized anxiety disorder (GAD) and osteoarthritis (OA) risk. Clinical data show a correlation, but the causal relationship between mental overload, GAD, and joint OA needs more study.
Area of Science:
- Genetics and Epidemiology
- Rheumatology
- Psychiatry
Background:
- Generalized anxiety disorder (GAD) is increasingly recognized, and its potential impact on physical health conditions like osteoarthritis (OA) warrants investigation.
- Osteoarthritis, particularly of weight-bearing joints (hip and knee), is a leading cause of disability.
- Understanding the interplay between mental health and joint disease is crucial for comprehensive patient care.
Purpose of the Study:
- To investigate the potential causal relationship between generalized anxiety disorder (GAD) stemming from mental overload and the risk of developing weight-bearing joint osteoarthritis (OA).
- To examine this relationship in both directions using bidirectional Mendelian randomization (MR) and clinical case analysis.
Main Methods:
- Bidirectional Mendelian randomization (MR) analyses were conducted using genome-wide association study (GWAS) summary statistics.
- Primary MR analysis employed the inverse-variance weighted (IVW) method, with sensitivity analyses using simple mode, weighted mode, MR-Egger regression, and weighted median.
- Clinical case data from patients undergoing hip/knee arthroplasty for OA were assessed using validated questionnaires.
Main Results:
- MR analyses revealed no statistically significant bidirectional causal effect between genetically predicted GAD and the risk of weight-bearing joint OA.
- Reverse MR analyses also found no evidence of a causal effect of weight-bearing joint OA on GAD.
- Clinical case evaluations indicated a high correlation between GAD and weight-bearing joint OA.
Conclusions:
- Mendelian randomization studies suggest that GAD due to mental overload does not causally increase the risk of hip or knee osteoarthritis.
- Despite the lack of a causal link in MR, clinical observations highlight a significant correlation between GAD and weight-bearing joint OA.
- Further research is necessary to clarify the complex relationship and potential underlying mechanisms connecting GAD from mental overload and weight-bearing joint OA.
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