Clinical and Translational Research
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2023; 29(44): 5872-5881
Published online Nov 28, 2023. doi: 10.3748/wjg.v29.i44.5872
Causal associations between inflammatory bowel disease and anxiety: A bidirectional Mendelian randomization study
Ying He, Chun-Lan Chen, Jian He, Si-De Liu
Ying He, Jian He, Si-De Liu, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Ying He, Department of Infectious Diseases, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
Chun-Lan Chen, Department of Pulmonary and Critical Care Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, Guangdong Province, China
Co-first authors: Ying He and Chun-Lan Chen.
Author contributions: He Y, Chen CL and Liu SD proposed the study conception and designed the study methods; He Y, Chen CL and He J contributed to the data acquisition/analysis; He Y and He J contributed to the statistical analysis/interpretation; Liu SD supervised and managed the whole research process; He Y, Chen CL drafted the original manuscript; Liu SD reviewed and revised the original manuscript; all authors have read and approve the final manuscript. He Y and Chen CL contributed equally to this work; they were designated as co-first authors because they made equal and substantial contributions to the study conception, design, data analysis, and manuscript preparation and editing, each playing key roles in ensuring the integrity and quality of the manuscript.
Supported by China Postdoctoral Science Foundation, No. 2021M701614; Guangdong Basic and Applied Basic Research Foundation, No. 2022A1515111063 and No. 2022A1515111045; Foundation of Guangdong Provincial People’s Hospital, No. 8200010545.
Institutional review board statement: The study used public GWAS statistics and did not collect new human data. Hence, ethical approval was not required by the ethics committee of Nanfang Hospital of Southern Medical University.
Clinical trial registration statement: As this study was not a clinical trial and did not involve any human studies, the clinical trial registration was not required for our research.
Informed consent statement: The study used public GWAS statistics and did not collect new human data. Hence, ethical approval was not required by the ethics committee of Nanfang Hospital of Southern Medical University.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: All GWAS summary data that support the findings of this study are openly available in the IIBDGC (https://www.ibdgenetics.org/), PGC (https://pgc.unc.edu/), and FinnGen project (https://www.finngen.fi/en).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Si-De Liu, PhD, Professor, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong Province, China. liuside2011@163.com
Received: October 8, 2023
Peer-review started: October 8, 2023
First decision: November 1, 2023
Revised: November 6, 2023
Accepted: November 14, 2023
Article in press: November 14, 2023
Published online: November 28, 2023
Processing time: 50 Days and 14.2 Hours
ARTICLE HIGHLIGHTS
Research background

Inflammatory bowel disease (IBD), mainly consisted of Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease. Depression and anxiety are common co-occurrence in IBD. A recent Mendelian randomization (MR) study has inferred the causal effect of depression on IBD, while the causality between IBD and anxiety has not been investigated.

Research motivation

Previous observational studies showed that IBD patients had a significantly higher incidence and risk of anxiety. Despite the existing findings demonstrated the bidirectional relationship between IBD and anxiety, the causal association between them remain unclear. This study seeks to find out causal association between IBD and anxiety from the genetic perspective by using MR analysis, potentially offering new insights into the pathogenesis and clinical significance of anxiety in IBD.

Research objectives

The study aims to investigate the causal relationship between IBD and anxiety by performing bidirectional MR analysis, to better understand the gene susceptibility of anxiety in IBD.

Research methods

Single nucleotide polymorphisms retrieved from genome-wide association studies (GWAS) were identified as instrument variants. GWAS statistics for UC and CD were obtained from the International IBD Genetics Consortium. GWAS statistics for anxiety were obtained from the Psychiatric Genomics Consortium and FinnGen project. Inverse-variance weighted was applied to assess the causal relationship, and the results were strengthened by sensitivity analyses.

Research results

This study found that the genetic susceptibility to UC was associated with the increased risk of anxiety [odds ratio: 1.071 (95% confidence interval: 1.009, 1.135), P = 0.023]; while genetic susceptibility to CD was not associated with anxiety. However, genetic susceptibility to anxiety was not associated with UC or CD. No heterogeneity and pleiotropy were found and leave-one-out analysis excluded the potential influence of a particular variant.

Research conclusions

This study identified that the genetic susceptibility to UC was significantly associated with anxiety, and provided the insight that early screening for the trait of anxiety is important for patients with UC.

Research perspectives

Although this study investigated the causal relationship between IBD and anxiety, the precise biological mechanisms by which UC affects the development of anxiety remain unclear, such as whether and how the gut-brain axis plays a role in this process. Hence, more basic and clinical studies are needed for the identification of key regulators and pathways to further uncover the biological mechanisms.