Decoding Autism Spectrum Disorder: A Network Biology Approach to Identifying Influential Genes and Their Functional Roles

ABSTRACT

Autism spectrum disorders (ASD) are a multifactorial neurodevelopmental condition driven by complex genetic interactions. While numerous ASD‐associated genes have been identified, their network‐level functional organization and developmental dynamics remain obscure. A gene co‐expression protein‐protein interaction (PPI) network using known ASD‐associated genes was constructed to identify topologically influential hub genes. Their functional characterization and spatiotemporal expression profiles were analyzed across multiple developmental stages and brain regions. Our analysis identified CTNNB1, GRIN2B, NRXN1, GRIA1, GRIA2, MAPK3, and ACTB as highly linked central genes, significantly enriched at postsynapses, and contributing to synaptic signaling, neurodevelopment, and ion transport. These genes, notably GRIN2B and NRXN1, exhibited peak expression during mid‐fetal stages. Our integrative analysis demonstrates that ASD is likely driven by a core set of functionally linked genes active during key developmental windows. Their disruption may compromise synaptic organization, contributing to ASD pathogenesis. Our findings provide a framework for identifying diagnostic and therapeutic molecular targets for ASD.