Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Mar 6, 2024; 12(7): 1215-1226
Published online Mar 6, 2024. doi: 10.12998/wjcc.v12.i7.1215
Investigating the causal associations between five anthropometric indicators and nonalcoholic fatty liver disease: Mendelian randomization study
Xian-Pei Xiao, Yong-Jun Dai, Yu Zhang, Meng Yang, Jian Xie, Guo Chen, Zheng-Jun Yang
Xian-Pei Xiao, Yu Zhang, Meng Yang, Jian Xie, Zheng-Jun Yang, Department of Oncology, Luojiang District People's Hospital of Deyang City, Deyang 618000, Sichuan Province, China
Yong-Jun Dai, Department of Orthopaedics, Luojiang District People's Hospital of Deyang City, Deyang 618000, Sichuan Province, China
Guo Chen, Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medical, Chengdu 610500, Sichuan Province, China
Co-first authors: Xian-Pei Xiao and Yong-Jun Dai.
Co-corresponding authors: Zheng-Jun Yang and Guo Chen.
Author contributions: Xiao XP and Dai YJ conceived and designed the study; Zhang Y and Yang M conducted preliminary analysis of the original data; Dai YJ and Xie J completed the drawing of the charts; Xiao XP, Dai YJ, Zhang Y and Yang M performed data analysis and result validation; Xiao XP wrote the paper. All authors read and approved the final manuscript. Xiao XP proposed, designed this study, conducted data analysis, and wrote the first draft of the paper. Dai YJ participated in proposing, designing this study, performing data analysis, and drawing graphs. Both authors have made vital and integral contributions to the completion of the project and are therefore eligible to be co-first authors of the paper. As co-corresponding authors, Yang ZJ and Chen G played an important and indispensable role in experimental design, data interpretation, and manuscript preparation. Funding for this project was applied for and obtained by Chen G. Yang ZJ conceived, designed and supervised the entire project process. The collaboration of Yang ZJ and Chen G was critical to the publication of this and other manuscripts still in preparation.
Supported by Science and Technology Research Project of Sichuan Administration of Traditional Chinese Medicine, No. 2023MS419.
Institutional review board statement: No need for ethical approval as used of anonymous open data.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data and material that support the findings of this study are available from public datasets that could be found in IEU OPEN GWAS and FinnGen research project.
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: Zheng-Jun Yang, MD, Doctor, Department of Oncology, Luojiang District People's Hospital of Deyang City, No. 286 Wanan South Road, Deyang 618000, Sichuan Province, China. 850006775@qq.com
Received: October 25, 2023
Peer-review started: October 25, 2023
First decision: December 31, 2023
Revised: January 14, 2024
Accepted: February 6, 2024
Article in press: February 6, 2024
Published online: March 6, 2024
Processing time: 127 Days and 14.4 Hours
Abstract
BACKGROUND

Although the etiology of nonalcoholic fatty liver disease (NAFLD) has not been thoroughly understood, the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence.

AIM

To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization (MR) design.

METHODS

The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators, including hip circumference (HC), waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), and body fat percentage (BF). Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium. Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables. Univariable MR (UVMR) and multivariable MR (MVMR) designs with analytical approaches, including inverse variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode methods, were used to assess the causal relationships between anthropometric indicators and NAFLD.

RESULTS

Causal relationships were revealed by UVMR, indicating that a higher risk of NAFLD was associated with a per-unit increase in WC [IVW: odds ratio (OR) = 2.67, 95%CI: 1.42-5.02, P = 2.25 × 10−3], and BF was causally associated with an increased risk of NAFLD (WM: OR = 2.23, 95%CI: 1.07-4.66, P = 0.033). The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking. However, no causal association between BF and NAFLD was observed. In addition, other causal relationships of HC, WHR (BMI adjusted), and BMI with the risk of NAFLD were not retained after FDR correction.

CONCLUSION

This study establishes a causal relationship, indicating that an increase in WC is associated with a higher risk of NAFLD. This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.

Keywords: Anthropometric indicator; Waist circumference; Nonalcoholic fatty liver disease; Mendelian randomization; Genetic variant

Core Tip: Previous studies have demonstrated the potential significance of anthropometric indicators in the development of nonalcoholic fatty liver disease (NAFLD). Nevertheless, inconsistencies exist in the results of these studies, and the causal association remains unclear. Abdominal obesity, measured by waist circumference (WC), is a risk factor for NAFLD, as demonstrated by previous studies. Nevertheless, many of these studies were cross-sectional or considered only a single measurement, neglecting a comprehensive evaluation of changes in WC over time and the effect of long-term development and lifestyle changes. Consequently, establishing a causal relationship between anthropometric indicators and NAFLD requires further robust evidence.