Patients with GERD are more prone to experience comorbid anxiety disorders or depression as a result of a causal relationship, according to findings from a recent publication in Frontiers in Psychiatry.

In this study, researchers conducted a bidirectional Mendelian randomization (MR) study to ascertain the causal relationship between GERD and anxiety disorders and depression. The scientists utilized summary statistics from genome-wide association studies (GWAS) in European individuals for this study.

To evaluate causality, the primary analytical method employed was the inverse-variance weighted (IVW) method. In addition, to supplement the IVW results, researchers utilized five added MR methods, including maximum likelihood, MR-Egger, weighted median, robust adjusted profile score [MR-RAPS], and mode-based estimate [MR-MBE]).

Additionally, numerous sensitivity analyses were executed to evaluate heterogeneity, horizontal pleiotropy, and stability, and a multivariable MR (MVMR) analysis was completed to ascertain the causal relationship by adjusting for potential confounders.

Researchers gathered data from a recent GWAS and evaluated 129,080 European patients with GERD and 473,524 healthy controls. Researchers also compiled genomic data from the FinnGen consortium R8 release, and data for anxiety disorders were obtained from 290,361 individuals (35,385 anxiety cases and 254,976 controls), while the data for depression came from 338,111 individuals (38,225 depression cases and 299,886 healthy controls).  

Results revealed that GERD substantially augments the risk for anxiety disorders (odds ratio [OR], 1.35; 95% CI, 1.15-1.59; P = .000225) and depression (OR, 1.32; 95% CI, 1.15-1.52; P = .000126). These results remained independent from confounding influences, as evidenced by a multivariable MR analysis.

Compared with the IVW results, the MR results of maximum likelihood, MR-Egger, weighted median, MR-RAPS, and MR-MBE remained comparable. The authors noted that sensitivity analysis implied the associations were strong, with no pleiotropy or heterogeneity noticed.

In contrast, when the researchers performed a reverse MR analysis, they discovered that anxiety and depression did not raise the risk for GERD. Lastly, MVMR analysis revealed that the effect of GERD on expanding the risk of anxiety disorders or depression was independent of confounders, such as smoking, alcohol use, and BMI.

The authors wrote, “To our knowledge, this is the first study to explore the causal association between GERD and anxiety disorders/depression by conducting an MR analysis with large-scale GWAS summary-level data, which enriched and refined the results of previous related findings.”

The authors noted that their MR study supports a causal association between GERD and an augmented risk of anxiety disorders and depression.

Based on their findings, the authors also concluded, “We have provided evidence that genetically predicted GERD increases the risk of anxiety disorders and depression. Therefore, symptomatic treatment for GERD patients should be accompanied by adequate psychological support to avoid the development of anxiety disorders and depression.”

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