Patients with gastroesophageal reflux disease (GERD) are more likely to develop comorbid anxiety disorders or depression due to a causal association, according to study findings published in Frontiers in Psychiatry.
Many observational studies in the scientific literature suggest a connection between GERD and anxiety and depression disorders; however, they are unable to indicate cause and effect.
As a solution, Mendelian randomization analysis detects single-nucleotide polymorphisms (SNPs) associated with a particular exposure, such as GERD. Genetic variants negate confounding variables and possible reverse causation because genetic variants precede disease manifestations. This method also overcomes unethical randomized control trials when attempting to determine the causal association between 2 diseases.
Researchers conducted a bidirectional Mendelian randomization study to assess the causal relationship between GERD exposure and the outcome of anxiety or depression.
They obtained data from a recent genome-wide association meta-analysis study (GWAS) analyzing 129,080 European patients with GERD compared with 473,524 healthy controls. Researchers also gathered genomic data from the FinnGen consortium R8 release on 35,385 people with anxiety disorders compared with 254,976 healthy controls and 38,225 people with depression compared with 299,886 healthy controls.
The first step in the Mendelian randomization analysis involved screening for instrumental variables that might influence development of GERD, anxiety, and depression. SNPs associated with confounding variables, such as smoking, alcohol consumption, and body mass index (BMI) were excluded from the instrumental variables, which must remain independent from all confounders.
Next, they conducted multiple types of sensitivity analyses to confirm that causal inferences were not biased by reverse causality. These sensitivity analyses indicated that the results of the study were strong without heterogeneity or pleiotropy present.
Based on the Mendelian randomization results, the researchers found that GERD significantly increases 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 Mendelian randomization analysis.
In contrast, when the researchers performed a reverse Mendelian randomization analysis, they discovered that anxiety and depression did not increase risk for GERD.
“This MR study supports a causal association between GERD and an increased risk of anxiety disorders and depression,” the study authors noted. “Therefore, complementing symptomatic treatment of GERD with psychological assessment and necessary psychological support therapy may help reduce the risk of future anxiety disorders and depression.”
Study limitations include lack of generalizability outside of the European population, lack of a stratified analysis based on age and gender due to data limitations, and the inability to confirm that the study findings were entirely independent of the horizontal polymorphism effect, although the sensitivity analyses indicated the reliability of the study’s findings.
Zeng Y, Cao S, Yang H. The causal role of gastroesophageal reflux disease in anxiety disorders and depression: a bidirectional Mendelian randomization study. Front Psychiatry. Published online February 22, 2023. doi:10.3389/fpyst.2023.1135923
This article originally appeared on Gastroenterology Advisor