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Meta-Analysis
. 2022 Nov 2;13(11):2010.
doi: 10.3390/genes13112010.

Bidirectional Association between Major Depressive Disorder and Gastroesophageal Reflux Disease: Mendelian Randomization Study

Yuyang Miao  1   2 , Shuai Yuan  3 , Ye Li  1   2 , Jie Chen  4   5 , Xue Li  6   7 , Susanna C Larsson  3   8 , Qiang Zhang  1   2
Affiliations
Meta-Analysis

Bidirectional Association between Major Depressive Disorder and Gastroesophageal Reflux Disease: Mendelian Randomization Study

Yuyang Miao et al. Genes (Basel). .

Abstract

Background: Observational research has found a bidirectional relationship between major depressive disorder and gastroesophageal reflux disease; however, the causal association of this relationship is undetermined.

Aims: A bidirectional Mendelian randomization study was performed to explore the causal relationships between major depressive disorder and gastroesophageal reflux disease.

Methods: For the instrumental variables of major depressive disorder and gastroesophageal reflux disease, 31 and 24 single-nucleotide polymorphisms without linkage disequilibrium (r2 ≤ 0.001) were selected from relevant genome-wide association studies, respectively, at the genome-wide significance level (p ≤ 5 × 10-8). We sorted summary-level genetic data for major depressive disorder, gastroesophageal reflux disease, gastroesophageal reflux disease without esophagitis, and reflux esophagitis from meta-analysis study of genome-wide association studies involving 173,005 individuals (59,851 cases and 113,154 non-cases), 385,276 individuals (80,265 cases and 305,011 non-cases), 463,010 individuals (4360 cases and 458,650 non-cases), and 383,916 individuals (12,567 cases and 371,349 non-cases), respectively.

Results: Genetic liability to major depressive disorder was positively associated with gastroesophageal reflux disease and its subtypes. Per one-unit increase in log-transformed odds ratio of major depressive disorder, the odds ratio was 1.31 (95% confidence interval [CI], 1.19-1.43; p = 1.64 × 10-8) for gastroesophageal reflux disease, 1.51 (95% CI, 1.15-1.98; p = 0.003) for gastroesophageal reflux disease without esophagitis, and 1.21 (95% CI, 1.05-1.40; p = 0.010) for reflux esophagitis. Reverse-direction analysis suggested that genetic liability to gastroesophageal reflux disease was causally related to increasing risk of major depressive disorder. Per one-unit increase in log-transformed odds ratio of gastroesophageal reflux disease, the odds ratio of major depressive disorder was 1.28 (95% confidence interval, 1.11-1.47; p = 1.0 × 10-3).

Conclusions: This Mendelian randomization study suggests a bidirectional causal relationship between major depressive disorder and gastroesophageal reflux disease.

Keywords: Mendelian randomization analysis; gastroesophageal reflux disease; major depressive disorder.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The present study design overview. All individuals are of European ancestry. MDD, Major Depressive Disorder; GERD, gastroesophageal reflux disease; SNP, single-nucleotide polymorphism.
Figure 2
Figure 2
Associations of MDD with risk of GERD in MR analyses. The ORs of GERD were scaled to a 1-unit increase in log OR of MDD. IVW, inverse variance weighted; OR, odds ratio; CI, confidence interval; MR, Mendelian randomization.
Figure 3
Figure 3
Associations of MDD with risk of GERD phenotypes in MR analyses. The ORs of GERD phenotypes were scaled to a 1-unit increase in log OR of MDD. IVW, inverse variance weighted; OR, odds ratio; CI, confidence interval; MR, Mendelian randomization.
Figure 4
Figure 4
Associations of GERD with risk of MDD in MR analyses. The ORs of MDD were scaled to a 1-unit increase in log OR of GERD. IVW, inverse variance weighted; OR, odds ratio; CI, confidence interval; MR, Mendelian randomization.
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