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已发表论文
处方止痛药使用与纤维肌痛风险之间的遗传关联：一项双向和多变量孟德尔随机化分析
Authors Zhou G, Cao W, Liang S, Ye Z, Liu Z, Zou W
Received 26 May 2025
Accepted for publication 14 October 2025
Published 16 October 2025 Volume 2025:18 Pages 5455—5465
DOI https://doi.org/10.2147/JPR.S526655
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Timothy Atkinson
Gaojie Zhou,1,* Wei Cao,1,* Shuang Liang,1 Ziyu Ye,1 Zhuoyi Liu,1 Wangyuan Zou1,2
1Department of Anesthesiology, Xiangya Hospital, Central South University, Hunan Province Clinical Research Center for Anesthesia and Perioperative Medicine, Changsha, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Wangyuan Zou, Department of Anesthesiology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, People’s Republic of China, Tel/Fax +86-731-84327413, Email wangyuanzou@csu.edu.cn
Introduction: Increasing evidence has indicated that prescription opioid use is associated with poor prognosis in patients with fibromyalgia. However, it remains unknown whether there are causal associations between prescription opioid and fibromyalgia.
Methods: We performed a bidirectional two-sample MR analysis using genetic variants associated with prescription pain medication use and fibromyalgia from genome-wide association studies (GWAS). Multivariable Mendelian randomization (MVMR) was further employed to ascertain the causal relationship, incorporating confounders such as major depressive disorder (MDD), anxiety disorders (ADs) and insomnia. A mediation MR analysis was conducted to assess their potential mediating roles.
Results: The forward two-sample Mendelian analysis revealed a positive causal role in the contribution of prescription opioid use to fibromyalgia, as indicated by the Inverse Variance Weighted (IVW) method (OR = 1.42, 95% CI: 1.17, 1.72, p = 3.55E-04) and the Weighted Median method (OR = 1.40, 95% CI: 1.07, 1.83; p = 0.01). In MVMR, the association remained after accounting for MDD, ADs and insomnia, none of which exhibited mediating effects. In the reverse MR analysis, which assessed whether fibromyalgia causally affected prescription opioid use, no significant associations were found. No substantial associations were observed between non-opioid pain medications and fibromyalgia.
Conclusion: Our findings provide genetic evidence supporting causal relationship for prescription opioid use on a high risk of fibromyalgia. This association remains robust after adjustment for MDD, ADs and insomnia. Given the potential for opioid prescriptions to increase the risk of developing fibromyalgia, clinicians should prioritize alternative, evidence-based pain management strategies.
Keywords: fibromyalgia, opioids, Mendelian randomization, genome-wide association studies
1Department of Anesthesiology, Xiangya Hospital, Central South University, Hunan Province Clinical Research Center for Anesthesia and Perioperative Medicine, Changsha, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Wangyuan Zou, Department of Anesthesiology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, People’s Republic of China, Tel/Fax +86-731-84327413, Email wangyuanzou@csu.edu.cn
Introduction: Increasing evidence has indicated that prescription opioid use is associated with poor prognosis in patients with fibromyalgia. However, it remains unknown whether there are causal associations between prescription opioid and fibromyalgia.
Methods: We performed a bidirectional two-sample MR analysis using genetic variants associated with prescription pain medication use and fibromyalgia from genome-wide association studies (GWAS). Multivariable Mendelian randomization (MVMR) was further employed to ascertain the causal relationship, incorporating confounders such as major depressive disorder (MDD), anxiety disorders (ADs) and insomnia. A mediation MR analysis was conducted to assess their potential mediating roles.
Results: The forward two-sample Mendelian analysis revealed a positive causal role in the contribution of prescription opioid use to fibromyalgia, as indicated by the Inverse Variance Weighted (IVW) method (OR = 1.42, 95% CI: 1.17, 1.72, p = 3.55E-04) and the Weighted Median method (OR = 1.40, 95% CI: 1.07, 1.83; p = 0.01). In MVMR, the association remained after accounting for MDD, ADs and insomnia, none of which exhibited mediating effects. In the reverse MR analysis, which assessed whether fibromyalgia causally affected prescription opioid use, no significant associations were found. No substantial associations were observed between non-opioid pain medications and fibromyalgia.
Conclusion: Our findings provide genetic evidence supporting causal relationship for prescription opioid use on a high risk of fibromyalgia. This association remains robust after adjustment for MDD, ADs and insomnia. Given the potential for opioid prescriptions to increase the risk of developing fibromyalgia, clinicians should prioritize alternative, evidence-based pain management strategies.
Keywords: fibromyalgia, opioids, Mendelian randomization, genome-wide association studies