ABSTRACT
Hundreds of genes are implicated as risk factors for autism spectrum disorder (ASD). However, the mechanisms through which they are associated with ASD remain unclear. Here, we analyzed transcriptomics from ASD toddlers and discovered a core gene network with dysregulated gene co-expression. The identified network includes highly expressed processes in fetal-stage brain development and is dysregulated in neuron models of ASD. We found ASD risk genes across diverse functions are upstream and regulate this core network. In particular, many risk genes impact the network through the RAS/ERK, PI3K/AKT, and WNT/β-catenin signaling pathways. Finally, the dysregulation degree of this network positively correlates with early-age ASD clinical severity. Thus, our results provide insights into how the heterogeneous genetic basis of ASD could converge on a core network with consequence on the postnatal outcome of toddlers with ASD. Deeper study into this may help decipher the molecular basis of ASD and decode the complex link between its genetic and phenotypic variation.