A study of genetic heterogeneity in autism spectrum disorders based on plasma proteomic and metabolomic analysis: multiomics study of autism heterogeneity

Abstract Genetic heterogeneity poses a challenge to research and clinical translation of autism spectrum disorder (ASD). In this study, we conducted a plasma proteomic and metabolomic study of children with ASD with and without risk genes ( de novo mutation) and controls to explore the impact of genetic heterogeneity on the search for biomarkers for ASD. In terms of the proteomic and metabolomic profiles, the groups of children with ASD carrying and those not carrying de novo mutation tended to cluster and overlap, and integrating them yielded differentially expressed proteins and differential metabolites that effectively distinguished ASD from controls. The mechanisms associated with them focus on several common and previously reported mechanisms. Proteomics results highlight the role of complement, inflammation and immunity, and cell adhesion. The main pathways of metabolic perturbations include amino acid, vitamin, glycerophospholipid, tryptophan, and glutamates metabolic pathways and solute carriers‐related pathways. Integrating the two omics analyses revealed that L‐glutamic acid and malate dehydrogenase may play key roles in the pathogenesis of ASD. These results suggest that children with ASD may have important underlying common mechanisms. They are not only potential therapeutic targets for ASD but also important contributors to the study of biomarkers for the disease.