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
Abstract
BACKGROUND

Anxiety is common in patients with inflammatory bowel disease (IBD), including those with ulcerative colitis (UC) and Crohn’s disease (CD); however, the causal relationship between IBD and anxiety remains unknown.

AIM

To investigate the causal relationship between IBD and anxiety by using bidirectional Mendelian randomization analysis.

METHODS

Single nucleotide polymorphisms retrieved from genome-wide association studies (GWAS) of the European population were identified as genetic instrument variants. GWAS statistics for individuals with UC (6968 patients and 20464 controls; adults) and CD (5956 patients and 14927 controls; adults) were obtained from the International IBD Genetics Consortium. GWAS statistics for individuals with anxiety were obtained from the Psychiatric Genomics Consortium (2565 patients and 14745 controls; adults) and FinnGen project (20992 patients and 197800 controls; adults), respectively. Inverse-variance weighted was applied to assess the causal relationship, and the results were strengthened by heterogeneity, pleiotropy and leave-one-out analyses.

RESULTS

Genetic susceptibility to UC was associated with an 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. Genetic susceptibility to anxiety was not associated with UC or CD. No heterogeneity or pleiotropy was observed, and the leave-one-out analysis excluded the potential influence of a particular variant.

CONCLUSION

This study revealed that genetic susceptibility to UC was significantly associated with anxiety and highlighted the importance of early screening for anxiety in patients with UC.

Keywords: Inflammatory bowel disease; Anxiety; Causal effect; Mendelian randomization; Genome-wide association studies

Core Tip: Our study provides evidence that genetic susceptibility to ulcerative colitis (UC) is associated with an increased risk of anxiety [odds ratio: 1.071 (95% confidence interval: 1.009, 1.135), P = 0.023], while genetic susceptibility to Crohn’s disease (CD) is not associated with an increased risk of anxiety. No causal effects of anxiety on UC and CD were observed in this study. In conclusion, our study demonstrates the causal effect of UC on anxiety. These findings may be helpful to increase physicians’ awareness of the need to recognize anxiety in UC patients and influence the management of anxiety in clinical practice.