Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 16, 2024; 12(14): 2359-2369
Published online May 16, 2024. doi: 10.12998/wjcc.v12.i14.2359
Genetically predicted fatty liver disease and risk of psychiatric disorders: A mendelian randomization study
Wei-Ming Xu, Hai-Fu Zhang, Yong-Hang Feng, Shuo-Jun Li, Bi-Yun Xie
Wei-Ming Xu, Department of Medicine, The First People's Hospital of Fuyang, Hangzhou 311400, Zhejiang Province, China
Hai-Fu Zhang, Yong-Hang Feng, Shuo-Jun Li, Bi-Yun Xie, Department of Internal Medicine, The First People's Hospital of Fuyang, Hangzhou 311400, Zhejiang Province, China
Co-first authors: Wei-Ming Xu and Hai-Fu Zhang.
Author contributions: Zhang HF and Xu WM conceived and designed the study; Li SJ and Feng YH collected data and performed data analysis; Zhang HF and Xu WM wrote the draft of this manuscript; Xu WM and Xie BY edited the manuscript.
Institutional review board statement: This study employed a Mendelian randomization design, and all the data were sourced from an open-access database; hence, these regulations were not applicable.
Informed consent statement: This study used only publicly available data, especially summary level data from GWAS, did not involve sensitive personal information, did not cause harm to individuals, and did not compromise their privacy; hence, these regulations were not applicable.
Conflict-of-interest statement: All authors have no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
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: Hai-Fu Zhang, MD, Doctor, Department of Internal Medicine, The First People's Hospital of Fuyang, No. 429 Beihuan Road, Fuchun Street, Hangzhou 311400, Zhejiang Province, China. 1375100541@qq.com
Received: January 8, 2024
Revised: February 18, 2024
Accepted: April 2, 2024
Published online: May 16, 2024
Abstract
BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ArLD) constitute the primary forms of chronic liver disease, and their incidence is progressively increasing with changes in lifestyle habits. Earlier studies have documented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.

AIM

To investigate the correlation between fatty liver and mental disorders, thus necessitating the implementation of a mendelian randomization (MR) study to elucidate this association.

METHODS

Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog, while information on mental disorders, including Alzheimer's disease, schizophrenia, anxiety disorder, attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder, multiple personality disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and schizophrenia was acquired from the psychiatric genomics consortium. A two-sample MR method was applied to investigate mediators in significant associations.

RESULTS

After excluding weak instrumental variables, a causal relationship was identified between fatty liver disease and the occurrence and development of some psychiatric disorders. Specifically, the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD (OR: 5.81, 95%CI: 5.59-6.03, P < 0.01), bipolar disorder (OR: 5.73, 95%CI: 5.42-6.05, P = 0.03), OCD (OR: 6.42, 95%CI: 5.60-7.36, P < 0.01), and PTSD (OR: 5.66, 95%CI: 5.33-6.01, P < 0.01). Meanwhile, NAFLD significantly increased the risk of developing bipolar disorder (OR: 55.08, 95%CI: 3.59-845.51, P < 0.01), OCD (OR: 61.50, 95%CI: 6.69-565.45, P < 0.01), and PTSD (OR: 52.09, 95%CI: 4.24-639.32, P < 0.01).

CONCLUSION

Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders, namely bipolar disorder, OCD, and PTSD, highlighting the significance of preventive measures against psychiatric disorders in patients with fatty liver disease.

Keywords: Non-alcoholic fatty liver disease, Alcohol-related liver disease, Psychiatric disorders, Mendelian randomization, Single nucleotide polymorphisms

Core Tip: Non-alcoholic fatty liver disease and alcohol-related liver disease are the predominant forms of chronic liver diseases, with their incidence gradually increasing due to changing lifestyle habits. Observational studies have indicated a potential association between fatty liver and psychiatric disorders, necessitating Mendelian randomization studies to elucidate this relationship. The findings revealed significant associations between genetic susceptibility to hepatic steatosis and an elevated risk of a wide spectrum of psychiatric disorders, including bipolar disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. These results underscore the imperative for preventive measures targeting mental health conditions in individuals with fatty liver disease.