Published online Jan 19, 2024. doi: 10.5498/wjp.v14.i1.88
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
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.
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.
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.
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.
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.
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.
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.