Mendel randomization confirmed gastroesophageal reflux disease may increase the risk of mental disorders.

Abstract

Background: The potential causal relationship between gastroesophageal reflux disease (GERD) and mental disorder was analyzed using the mendelian randomization (MR) method.

Methods: Data are derived from genome-wide association study (GWAS) summary data, using gastroesophageal reflux disease (GERD) as the exposure factor. Single nucleotide polymorphisms (SNPs) significantly associated with GERD were selected as instrumental variables (IVs), and mental disorders (bipolar disorder, major depression, Alzheimer's disease, anorexia nervosa, anxiety, and obsessive-compulsive disorder) were used as outcome variables. The inverse variance weighted (IVW) method is used as the main analysis method, and MR-Egger regression, weighted median (WM) method, simple mode and weighted mode are used as supplementary methods for Mendelian randomization (MR) analysis. Cochran's Q test and P value are used to quantify heterogeneity, MR-Egger regression was used to evaluate the multilevel effect test of SNPs, and leave-one-out method to determine whether there are potential SNPs, and to evaluate the stability of the results. Odds ratio (OR) and 95% confidence interval (CI) were used as effect indicators to evaluate whether there is a causal relationship between GERD and mental disorders.

Results: IVW demonstrated a causal relationship between GERD and bipolar disorder (OR = 1.70, 95%CI = 1.39-2.09, P < 0.05) and anorexia nervosa (OR = 0.71, 95%CI = 0.52-0.99, P < 0.05). Furthermore, there is a weak causal relationship between GERD and major depression (OR = 1.01, 95%CI = 1.01-1.02, P < 0.05) and anxiety (OR = 1.01, 95%CI = 1.01-1.01, P < 0.05). Similarly, there is no evidence of a causal relationship between GERD and Alzheimer's disease (OR = 0.95, 95%CI = 0.87-1.03, P > 0.05) or obsessive-compulsive disorder (OR = 0.95, 95%CI = 0.67-1.36, P > 0.05). Cochran's Q test for heterogeneity shows that there is no significant heterogeneity (P > 0.05) for bipolar disorder, anxiety, and obsessive-compulsive disorder. However, major depression, Alzheimer's disease, and anorexia nervosa have some degree of heterogeneity (P < 0.05). Horizontal pleiotropic analysis showed that the P values for six mental disorders (0.750, 0.296, 0.154, 0.798, 0.893, 0.451) were all greater than 0.05. Leave-one-out analysis and funnel plot showed that MR analysis results can be considered relatively stable. All F are > 10, indicating no weak IVs bias.

Conclusion: GERD can obviously increase the risk of bipolar disorder; the increased risk of anxiety disorder is very slight. There is no clear evidence to support the causal relationship between GERD and four other mental disorders, including major depression, Alzheimer's disease, anorexia nervosa, and obsessive-compulsive disorder.