AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO026030030
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ORIGINAL RESEARCH ARTICLE

Intervertebral disc degeneration and generalized anxiety disorder: A bidirectional two-sample Mendelian randomization study

Wei Zhang1† ,  Jiantong Wei1,2† ,  Shenggang Xu3 ,  Ying Cao1 ,  Xiaomei Yang1*
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1 Department of Orthopedics, Zhangye People’s Hospital Affiliated to Hexi University, Zhangye, Gansu, China
2 Frontier Innovation Research Center, First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
3 Department of Public Health, Medical College of Hexi University, Zhangye, Gansu, China
†These authors contributed equally to this work.
EJMO, 026030030 https://doi.org/10.36922/EJMO026030030
Received: 15 January 2026 | Revised: 9 February 2026 | Accepted: 24 February 2026 | Published online: 29 April 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: The co-occurrence of chronic musculoskeletal conditions and psychiatric disorders is clinically significant; however, the causal direction between intervertebral disc degeneration (IVDD) and generalized anxiety disorder (GAD) remains poorly defined.

Objective: To evaluate the bidirectional causal association between IVDD and GAD using Mendelian randomization (MR).

Methods: Leveraging aggregate statistics from extensive genome-wide association study (GWAS) datasets, we performed a two-sample bidirectional MR investigation. Genetic proxies serving as instrumental variables (IVs) were identified using stringent filtering criteria, including a significance threshold of p < 5 × 10−8, and the exclusion of linkage disequilibrium (r2 < 0.001, distance > 10,000 kb). The primary causal effect was quantified using inverse variance-weighted (IVW) regression, while robustness of the estimates was cross-validated using MR-Egger, weighted median, and model-based estimators. To ensure the integrity of the inference, we performed sensitivity diagnostics, including Cochran’s Q test for heterogeneity, the MR-Egger intercept for directional pleiotropy, and leave-one-out analysis for individual single-nucleotide polymorphism stability.

Results: In the forward-direction analysis, a genetic predisposition to IVDD was correlated with an increased risk of GAD, as confirmed by both the IVW model (odds ratio [OR] = 1.198, 95% confidence interval [CI]: 1.069–1.343, p = 0.002) and the weighted median method (OR = 1.193, 95% CI: 1.024–1.389, p = 0.023). In contrast, no statistically significant causal influence of GAD on the risk of IVDD was observed (p > 0.05). Comprehensive sensitivity analyses confirmed that the selected IVs satisfied the core MR assumptions. Furthermore, diagnostic tests revealed no evidence of substantial heterogeneity (Q p-value = 0.098) or significant bias stemming from horizontal pleiotropy (Egger intercept p-value = 0.568).

Conclusion: Bidirectional MR analysis supports a unidirectional causal relationship from IVDD to GAD, underscoring the importance of routine anxiety screening and targeted psychological interventions in patients with spinal degeneration to mitigate subsequent psychiatric deterioration.

Keywords
Intervertebral disc degeneration
Generalized anxiety disorder
Mendelian randomization
Causality
Funding
This project was supported by the Hexi University President’s Fund for Innovative Research Teams (CXTD002, 2022), the Hexi University President’s Fund for Young Researchers (QN2024031, 2024), the Gansu Provincial Health and Health Industry Science and Technology Innovation Major Research Project (GSWSQN2024-21, 2024), and the Gansu Provincial Science and Technology Plan Funding Project (25JRRG006, 2025), and the Gansu Provincial Department of Education Industrial Support Program Project (2025CYZC-061, 2025).
Conflict of interest
The authors have no conflicts of interest to disclose.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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