Abstract
A Mendelian randomization (MR) study was undertaken to establish a causal link between gastroesophageal reflux disease (GERD) and frozen shoulder (FS), examining whether the risk of GERD with FS is mediated through mood fluctuations. Genetic loci from populations of independent European ancestry were selected as instrumental variables for GERD, FS, and mood swings. The primary analysis employed the inverse-variance weighted method supplemented by 3 additional analytical methods. This was conducted using two-sample and two-step MR analyses. This study explored the correlation and mediating effects of mood swings between GERD and FS. Our study employed heterogeneity and horizontal diversity, and sensitivity analysis was conducted using the leave-one-out method to explore the robustness of the results. In the two-sample MR analysis, for every 1-unit increase in the log-transformed odds ratio (OR) of GERD, the corresponding OR increased to 1.844 (inverse-variance weighting: OR = 1.844, 95% confidence interval: 1.47-2.30, P < .001). In the two-step MR analysis, we found that mood swings played a mediating role in the association between GERD and FS. We assessed this mediating effect using the delta method (b = 0.181, SE = 0.059, OR = 1.199, 95% confidence interval: 1.072-1.349). Analysis of the data using the above methods indicated that GERD is a risk factor for FS, and mood swings mediate between the 2. Therefore, GERD and mood swings should be included in the health management of patients with FS.