Abstract
Hundreds of genes are implicated as risk factors for autism spectrum disorder (ASD). However, the mechanisms through which these genes exert their effects at early ages in ASD remain unclear. To identify such mechanisms, 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 core network through the RAS/ERK, PI3K/AKT, and WNT/B-catenin signaling pathways. Finally, the dysregulation degree of this core 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 enable deciphering the molecular basis of ASD and decode the complex link between its genetic and phenotypic variation.
Footnotes
Improve the quality of the figures and revised text
