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Depression and risk of gastrointestinal disorders: a comprehensive two-sample Mendelian randomization study of European ancestry

Published online by Cambridge University Press:  15 May 2023

Dongze Chen Open the ORCID record for Dongze Chen [Opens in a new window] ,
Yali Zhang ,
Tao Huang  and
Jinzhu Jia
Dongze Chen*
Affiliation:
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
Yali Zhang
Affiliation:
Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100083, China
Tao Huang
Affiliation:
Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, China Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing 100191 China
Jinzhu Jia*
Affiliation:
Department of Biostatistics, School of Public Health, Peking University, Beijing, China Center for Statistical Science, Peking University, Beijing, China
*
Corresponding author: Jinzhu Jia; Email: [email protected]; Dongze Chen; Email: [email protected]
Corresponding author: Jinzhu Jia; Email: [email protected]; Dongze Chen; Email: [email protected]
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Abstract

Background

Major depressive disorder (MDD) is clinically documented to co-occur with multiple gastrointestinal disorders (GID), but the potential causal relationship between them remains unclear. We aimed to evaluate the potential causal relationship of MDD with 4 GID [gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), peptic ulcer disease (PUD), and non-alcoholic fatty liver disease (NAFLD)] using a two-sample Mendelian randomization (MR) design.

Methods

We obtained genome-wide association data for MDD from a meta-analysis (N = 480 359), and for GID from the UK Biobank (N ranges: 332 601–486 601) and FinnGen (N ranges: 187 028–218 792) among individuals of European ancestry. Our primary method was inverse-variance weighted (IVW) MR, with a series of sensitivity analyses to test the hypothesis of MR. Individual study estimates were pooled using fixed-effect meta-analysis.

Results

Meta-analyses IVW MR found evidence that genetically predicted MDD may increase the risk of GERD, IBS, PUD and NAFLD. Additionally, reverse MR found evidence of genetically predicted GERD or IBS may increase the risk of MDD.

Conclusions

Genetically predicted MDD may increase the risk of GERD, IBS, PUD and NAFLD. Genetically predicted GERD or IBS may increase the risk of MDD. The findings may help elucidate the mechanisms underlying the co-morbidity of MDD and GID. Focusing on GID symptoms in patients with MDD and emotional problems in patients with GID is important for the clinical management.

Keywords

Gastroesophageal reflux diseaseirritable bowel syndromemajor depressive disorderMendelian randomizationnon-alcoholic fatty liver diseasepeptic ulcer disease
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 15 , November 2023 , pp. 7309 - 7321
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Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

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