Chen Menglin, Tu Houshu, Zhou Jiaoli, Zhang Yi, Wen Shuting, Xiao Yao, He Ling
School of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, 330004, People's Republic of China.
Gastroenterology Division, Jiangxi University of Chinese Medicine Affiliated Hospital, Nanchang, 330006, People's Republic of China.
J Pain Res. 2025 Jun 24;18:3107-3115. doi: 10.2147/JPR.S494166. eCollection 2025.
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.
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.
MR analysis showed that CWP increased the risk of developing GERD [N = 4, odds ratio (OR): 245.244; 95% confidence interval (CI): 4.35E+00,1.38E+04; =0.007 < 0.05] and vice versa (N = 28; OR:1.019; 95% CI: 1.009-1.029; = 0.029 < 0.05). Bidirectional evidence of causality existed. The sensitivity analysis demonstrated the robustness and reliability of the findings.
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.
既往观察性研究发现胃食管反流病（GERD）与慢性广泛性疼痛（CWP）之间存在关联。尽管如此，尚不清楚这两种疾病中哪一种（如果有的话）会引发另一种疾病。我们的研究将使用双向孟德尔随机化（MR）来评估它们之间的因果关系。
我们检查了来自全基因组关联研究（GWAS）的两组公开可用数据：GERD（129,080例病例和602,604例对照）和CWP（6,914例病例和242,929例对照）。我们使用逆方差加权（IVW）方法作为主要分析方法，但也进行了加权中位数和MR-Egger回归分析。我们进行了各种敏感性研究，以评估结论的一致性、水平多效性和稳定性。
MR分析表明，CWP会增加患GERD的风险 [N = 4，优势比（OR）：245.244；95%置信区间（CI）：4.35E+00，1.38E+04；P = 0.007 < 0.05]，反之亦然（N = 28；OR：1.019；95% CI：1.009 - 1.029；P = 0.029 < 0.05）。存在双向因果证据。敏感性分析证明了研究结果的稳健性和可靠性。
我们的研究证明了GERD与慢性广泛性疼痛之间存在双向因果关系，未来针对CWP的干预措施可能是预防或减轻GERD的有效策略，反之亦然。
