Peer-reviewedCC BY-NCJournal of pain research12 Oct 2026

C-Reactive Protein and Risk of Low Back Pain: A Univariable and Multivariable Mendelian Randomization Study.

Shalin Feng¹
Jun Mou²
Xiaoqin Wang³
Changping Mu³

¹Graduate School, North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China.
²Graduate School, China West Normal University, Nanchong, Sichuan, People's Republic of China.
³Department of Radiology, Chongqing Academy of Medical Sciences, Chongqing General Hospital, Chongqing University, Chongqing, People's Republic of China.

Abstract

Objective

To investigate the causal associations of genetically predicted C-reactive protein (CRP), major depressive disorder (MDD), body mass index (BMI), and smoking initiation with low back pain (LBP) using Mendelian randomization (MR).Methods

Summary-level GWAS data for exposures and LBP (FinnGen R8) were obtained. Instrumental variables were selected at a strict genome-wide threshold (P < 5×10⁻⁸) and harmonized. Two-sample univariable MR was performed primarily using random-effects inverse-variance weighted (IVW). Multivariable MR (MVMR) assessed independent effects adjusting for confounders, evaluated via conditional F-statistics. Sensitivity analyses included Cochran's Q, MR-Egger, and leave-one-out diagnostics.Results

Univariable MR showed that genetically predicted circulating CRP was associated with an increased risk of LBP (IVW: β = 0.100, 95% CI: 0.040 to 0.160, P = 0.001), corroborated by the weighted median estimator. Conversely, genetically predicted MDD showed no causal association with LBP (β = -0.039, P = 0.752). In MVMR, instrument strength was robust (conditional F: CRP = 61.37, BMI = 23.30, smoking = 14.39). Elevated CRP remained an independent risk factor for LBP (β = 0.093, 95% CI: 0.016 to 0.170, P = 0.018). Additionally, smoking initiation exhibited an independent causal effect (β = 0.268, 95% CI: 0.081 to 0.455, P = 0.005), while BMI showed no direct effect (β = 0.129, P = 0.128).Conclusion

This study provides genetic evidence consistent with an independent causal association between elevated CRP levels and LBP risk, alongside smoking initiation. Genetically predicted MDD and BMI did not exhibit independent causal effects on LBP.

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Cite

BibTeX RIS

BibTeX

@article{feng2026creactive,
  title = {{C-Reactive Protein and Risk of Low Back Pain: A Univariable and Multivariable Mendelian Randomization Study.}},
  author = {Shalin Feng and Jun Mou and Xiaoqin Wang and Changping Mu},
  journal = {Journal of pain research},
  year = {2026},
  month = oct,
  doi = {10.2147/jpr.s632857},
  url = {https://europepmc.org/article/MED/42890752},
  note = {CC BY-NC},
}

RIS

TY  - JOUR
TI  - C-Reactive Protein and Risk of Low Back Pain: A Univariable and Multivariable Mendelian Randomization Study.
AU  - Shalin Feng
AU  - Jun Mou
AU  - Xiaoqin Wang
AU  - Changping Mu
PY  - 2026
DA  - 2026/10/12
JO  - Journal of pain research
DO  - 10.2147/jpr.s632857
UR  - https://europepmc.org/article/MED/42890752
AB  - Objective  To investigate the causal associations of genetically predicted C-reactive protein (CRP), major depressive disorder (MDD), body mass index (BMI), and smoking initiation with low back pain (LBP) using Mendelian randomization (MR).Methods  Summary-level GWAS data for exposures and LBP (FinnGen R8) were obtained. Instrumental variables were selected at a strict genome-wide threshold (P < 5×10⁻⁸) and harmonized. Two-sample univariable MR was performed primarily using random-effects inverse-variance weighted (IVW). Multivariable MR (MVMR) assessed independent effects adjusting for confounders, evaluated via conditional F-statistics. Sensitivity analyses included Cochran's Q, MR-Egger, and leave-one-out diagnostics.Results  Univariable MR showed that genetically predicted circulating CRP was associated with an increased risk of LBP (IVW: β = 0.100, 95% CI: 0.040 to 0.160, P = 0.001), corroborated by the weighted median estimator. Conversely, genetically predicted MDD showed no causal association with LBP (β = -0.039, P = 0.752). In MVMR, instrument strength was robust (conditional F: CRP = 61.37, BMI = 23.30, smoking = 14.39). Elevated CRP remained an independent risk factor for LBP (β = 0.093, 95% CI: 0.016 to 0.170, P = 0.018). Additionally, smoking initiation exhibited an independent causal effect (β = 0.268, 95% CI: 0.081 to 0.455, P = 0.005), while BMI showed no direct effect (β = 0.129, P = 0.128).Conclusion  This study provides genetic evidence consistent with an independent causal association between elevated CRP levels and LBP risk, alongside smoking initiation. Genetically predicted MDD and BMI did not exhibit independent causal effects on LBP.
SN  - 1178-7090
ER  -

Abstract

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