Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Jan 19, 2024; 14(1): 88-101
Published online Jan 19, 2024. doi: 10.5498/wjp.v14.i1.88
Des-Arg(9) bradykinin as a causal metabolite for autism spectrum disorder
Zhong-Yu Huang, Zi-Pan Lyu, Hong-Gui Li, Hua-Zhi You, Xiang-Na Yang, Cai-Hui Cha
Zhong-Yu Huang, Center for Medical Research on Innovation and Translation, Institute of Clinical Medicine, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510000, Guangdong Province, China
Zi-Pan Lyu, School of Biological Sciences, Nanyang Technological University, Nanyang Ave 639798, Singapore
Hong-Gui Li, Department of Pediatrics, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
Hua-Zhi You, Department of Nutrition, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
Xiang-Na Yang, Department of Pediatric Traditional Chinese Medicine Clinic, Guangzhou Women and Children's Medical Center, Guangzhou 510632, Guangdong Province, China
Cai-Hui Cha, Department of Psychology, Guangzhou Women and Children's Medical Center, Guangzhou 510632, Guangdong Province, China
Co-first authors: Zhong-Yu Huang and Zi-Pan Lyu.
Author contributions: Huang ZY and Lyu ZP contributed toward the concept, data analysis, manuscript writing, manuscript review and funding; Li HG, You HZ, Yang XN and Cha CH contributed toward data collection, data analysis and manuscript review.
Supported by The Guangdong Basic and Applied Basic Research Foundation, No. 2023A1515011432; The Guangzhou Science and Technology Planning Project, No. 2023A04J0627; and National Natural Science Foundation of China, No. 82004256.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Guangzhou First People's Hospital (approval No. S-2022-208).
Informed consent statement: This study was carried out based on publicly available dataset that published by previous researches. Therefore, there’s no informed consent statement.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data used to support the findings of this study are available from the first author (mail:zy1717086@163.com) upon request.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: Zhong-Yu Huang, MD, PhD, Assistant Professor, Research Fellow, Center for Medical Research on Innovation and Translation, Institute of Clinical Medicine, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, No. 1 Panfu Road, Yuexiu District, Guangzhou 510000, Guangdong Province, China. zy1717086@163.com
Received: July 31, 2023
Peer-review started: July 31, 2023
First decision: November 1, 2023
Revised: November 8, 2023
Accepted: December 7, 2023
Article in press: December 7, 2023
Published online: January 19, 2024
Processing time: 172 Days and 7.5 Hours
ARTICLE HIGHLIGHTS
Research background

This study delves into the complex landscape of autism spectrum disorder (ASD), an early-onset neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. The etiology of ASD remains enigmatic, prompting a crucial need for robust diagnostic biomarkers. The study explores the potential interplay of genetic and environmental factors in ASD development, with a focus on plasma metabolites and their causal associations, providing a foundation for future advancements in diagnosis and intervention.

Research motivation

In the realm of ASD research, the pressing motivation lies in early diagnosis and effective therapeutic interventions. The study aims to tackle the pivotal challenge of identifying diagnostic biomarkers, given the intricate interplay of genetic and environmental factors in ASD etiology. A successful exploration of these causal associations can pave the way for innovative diagnostic tools and targeted interventions, offering hope for improved outcomes and quality of life for individuals with ASD.

Research objectives

This study sought to uncover the causal connections between plasma metabolites and ASD while accounting for genetic and environmental factors. The realized objective of identifying these associations carries profound implications for advancing diagnostic biomarkers and guiding future research in the field of ASD.

Research methods

This study employed a two-sample Mendelian randomization (MR) analysis, a robust method that harnessed data from large-scale genome-wide association studies on metabolites and ASD. Novelty lies in the integration of genetic variants as instrumental variables to estimate causal associations, and the innovative use of the inverse variant weight algorithm. These methods unveiled the potential role of plasma metabolites in ASD etiology, shedding new light on diagnostic biomarkers and therapeutic avenues.

Research results

Des-Arg(9)-bradykinin emerged as a compelling causal metabolite associated with an increased risk of ASD. The sensitivity analysis underscored the robustness of this association. Furthermore, the identification of five hub genes, including KNG1, F12, BDKRB1, CCNA2 and CDK2, signifies the potential involvement of these genes in the ASD-Des-Arg(9)-bradykinin association. Enrichment analysis shed light on a multitude of biological processes, from peptide GPCRs to immune system functions, offering a comprehensive insight into the potential mechanisms linking Des-Arg(9)-bradykinin with ASD.

Research conclusions

This study contributes novel insights by proposing Des-Arg(9)-bradykinin as a potential causal metabolite for ASD. The study set metabolites as proxy of genetic and environmental factors, and leveraged two-sample MR methods to elucidate the associations. These findings introduce new diagnostic and predictive biomarker for ASD, offering a promising pathway for future research and clinical practice.

Research perspectives

The direction of future research should focus on comprehensive investigations into the complex interplay of genetic and environmental factors in ASD etiology. Expanding datasets to include diverse populations and incorporating multi-omics approaches can provide a more nuanced understanding of ASD development. Additionally, future research should explore the identification of additional biomarkers and the underlying mechanisms, potentially paving the way for innovative diagnostic tools and personalized interventions to enhance the lives of individuals with ASD.