The Causal Correlation Between Gastroesophageal Reflux Disease and Chronic Widespread Pain: A Bidirectional Mendelian Randomization Study

Menglin Chen; Houshu Tu; Jiaoli Zhou; Yi Zhang; Shuting Wen; Yao Xiao; Ling He

doi:10.2147/JPR.S494166

The Causal Correlation Between Gastroesophageal Reflux Disease and Chronic Widespread Pain: A Bidirectional Mendelian Randomization Study

J Pain Res. 2025 Jun 24:18:3107-3115. doi: 10.2147/JPR.S494166. eCollection 2025.

Authors

Menglin Chen^{1

2}, Houshu Tu^{1

2}, Jiaoli Zhou^{1

2}, Yi Zhang^{1

2}, Shuting Wen^{1

2}, Yao Xiao^{1

2}, Ling He²

Affiliations

¹ School of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, 330004, People's Republic of China.
² Gastroenterology Division, Jiangxi University of Chinese Medicine Affiliated Hospital, Nanchang, 330006, People's Republic of China.

Abstract

Background: Previous observational research found a relationship between gastroesophageal reflux disease (GERD) and chronic widespread pain (CWP). Despite this, it is unknown which, if any, of the conditions produces the other. Our study will use bidirectional Mendelian randomization (MR) to evaluate their causal link.

Methods: We examined two sets of publically accessible data from genome-wide association studies (GWAS): GERD (129,080 cases and 602,604 controls) and CWP (6,914 cases and 242,929 controls). We used the inverse variance weighting (IVW) approach as the major analysis method, but we also ran weighted median and MR-Egger regression analyses. We performed various sensitivity studies to assess the conclusions' consistency, horizontal pleiotropy, and stability.

Results: MR analysis showed that CWP increased the risk of developing GERD [N_SNP = 4, odds ratio (OR): 245.244; 95% confidence interval (CI): 4.35E+00,1.38E+04; p =0.007 < 0.05] and vice versa (N_SNP = 28; OR:1.019; 95% CI: 1.009-1.029; p = 0.029 < 0.05). Bidirectional evidence of causality existed. The sensitivity analysis demonstrated the robustness and reliability of the findings.

Conclusion: Our study demonstrated a bidirectional causal relationship between GERD and chronic widespread pain, and future interventions for CWP may be an effective strategy for preventing or mitigating GERD and vice versa.

Keywords: Mendelian randomization; bidirectional; causal; chronic widespread pain; fibromyalgia; gastroesophageal reflux disease.