Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Jan 19, 2024; 14(1): 15-25
Published online Jan 19, 2024. doi: 10.5498/wjp.v14.i1.15
Association between inflammatory bowel disease and all-cause dementia: A two-sample Mendelian randomization study
Ou-Lan Liao, Si-Yuan Xie, Jun Ye, Qin Du, Guo-Chun Lou
Ou-Lan Liao, Si-Yuan Xie, Jun Ye, Qin Du, Guo-Chun Lou, Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Ou-Lan Liao, Qin Du, Department of Gastroenterology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, Zhejiang Province, China
Co-corresponding authors: Qin Du and Guo-Chun Lou.
Author contributions: Liao OL designed the study, acquired and analyzed data, and wrote the manuscript; Xie SY contributed to conceptualization and methodology; Ye J contributed to writing review and editing; Du Q and Lou GC designed, refined the study protocol, and supervised this study. All authors were involved in the critical review of the results and have contributed to, read, and approved the final manuscript. Du Q and Lou GC contributed equally to this work as co-corresponding authors. Firstly, both researchers were co-principal investigators of this study and have made equally significant contributions throughout the study process. Designating them as co-corresponding authors accurately reflects the allocation of responsibilities related to completing the study. Secondly, both researchers shared responsibility for ensuring the authenticity of the manuscript's content and credibility of its conclusions, as well as handling communication and consultation work. Therefore, we believe that designating Du Q and Lou GC as co-corresponding authors is appropriate, reflecting the collaborative spirit and equal contributions of our team.
Institutional review board statement: No institutional review board statement is required since this study was based on public databases.
Clinical trial registration statement: The data was from large sample size GWAS, and no Clinical Trial Registration Statement is required.
Informed consent statement: The data was from large sample size genome-wide association study, and no informed consent statement is required.
Conflict-of-interest statement: The authors have no conflict of interest to report.
Data sharing statement: The summary statistics of IBD, UC, and CD GWAS (IIBDGC) is available at https://gwas.mrcieu.ac.uk/datasets/ieu-a-31, https://gwas.mrcieu.ac.uk/datasets/ieu-a-32, and https://gwas.mrcieu.ac.uk/datasets/ieu-a-30, respectively. The summary data for the second IBD GWAS (UK Biobank) is provided at https://cnsgenomics.com/data/wu_et_al_2021_nc/5_IBD_summary. The summary statistics of all-cause dementia, dementia in AD, VaD, dementia in other diseases classified elsewhere, and unspecified dementia GWAS (FinnGen) is available at https://storage.googleapis.com/finngen-public-data-r7/summary_stats/finngen_R7_F5_DEMENTIA.gz, https://storage.googleapis.com/finngen-public-data-r7/summary_stats/finngen_R7_F5_ALZHDEMENT.gz, https://storage.googleapis.com/finngen-public-data-r7/summary_stats/finngen_R7_F5_VASCDEM.gz, https://storage.googleapis.com/finngen-public-data-r7/summary_stats/finngen_R7_F5_DEMINOTH.gz, and https://storage.googleapis.com/finngen-public-data-r7/summary_stats/finngen_R7_F5_DEMNAS.gz, respectively. All datasets were downloaded on 2023-7-11.
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: Qin Du, MBBS, Chief Physician, Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China. duqin@zju.edu.cn
Received: November 7, 2023
Peer-review started: November 7, 2023
First decision: November 23, 2023
Revised: December 3, 2023
Accepted: December 26, 2023
Article in press: December 26, 2023
Published online: January 19, 2024
ARTICLE HIGHLIGHTS
Research background

Evidence from observational studies has not been able to establish a causal link between inflammatory bowel disease (IBD) and dementia.

Research motivation

Gut homeostasis is implicated in many psychiatric and neurological disorders through the bidirectional microbiome-gut-brain axis.

Research objectives

The aim was to find out whether IBD was causally related to all-cause dementia.

Research methods

Based on the publicly available genome-wide association study data from large population, multiple methods of Mendelian randomization (MR) were performed to estimate the effects of genetically predicted IBD on dementia, and inverse variance weighted was considered as the primary analysis. MR egger intercept, MR pleiotropy residual sum and outlier, and Cochran's Q test were used to test pleiotropy and heterogeneity.

Research results

No evidence for a causal effect of IBD on dementia risk was found in three MR methods of MR, which was consistent with validation analyses. Furthermore, MR analysis suggested that IBD and subentities did not causally affect all-cause dementia and its four subtypes.

Research conclusions

Our MR study found no association between the risk of all-cause dementia and genetically predicted IBD.

Research perspectives

Genetically predicted IBD is not associated with all-cause dementia risk, and dementia prevention interventions for patients with IBD can be similar to those in healthy populations.