TY - JOUR
T1 - Bidirectional Association between Major Depressive Disorder and Gastroesophageal Reflux Disease
T2 - Mendelian Randomization Study
AU - Miao, Yuyang
AU - Yuan, Shuai
AU - Li, Ye
AU - Chen, Jie
AU - Li, Xue
AU - Larsson, Susanna C
AU - Zhang, Qiang
N1 - Funding Information:
This study was funded by Major Research Plan of National Natural Science Foundation of China (Grant No.92163213) and General Program of National Natural Science Foundation of China (Grant No. 81970085).
Publisher Copyright:
© 2022 by the authors.
PY - 2022/11/2
Y1 - 2022/11/2
N2 - 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.
AB - 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.
KW - Humans
KW - Depressive Disorder, Major/epidemiology
KW - Genome-Wide Association Study
KW - Mendelian Randomization Analysis
KW - Esophagitis, Peptic
KW - Gastroesophageal Reflux/epidemiology
U2 - 10.3390/genes13112010
DO - 10.3390/genes13112010
M3 - Article
C2 - 36360247
VL - 13
JO - Genes
JF - Genes
SN - 2073-4425
IS - 11
M1 - 2010
ER -