Shared Pathways Among Autism Candidate Genes Determined by Co-expression Network Analysis of the Developing Human

# The Author(s) 2015. This article is published with open access at Springerlink.com Abstract Autism spectrum disorder (ASD) is a neuro-developmental syndrome known to have a significant but com-plex genetic etiology. Hundreds of diverse genes have been implicated in ASD; yet understanding how many genes, each with disparate function, can all be linked to a single clinical phenotype remains unclear. We hypothesized that understand-ing functional relationships between autism candidate genes during normal human brain development may provide conver-gent mechanistic insight into the genetic heterogeneity of ASD. We analyzed the co-expression relationships of 455 genes pre-viously implicated in autism using the BrainSpan human tran-scriptome database, across 16 anatomical brain regions span-ning prenatal life through adulthood. We discovered modules of ASD candidate genes with biologically relevant temporal co-expression dynamics, which were enriched for functional ontologies related to synaptogenesis, apoptosis, and GABA-ergic neurons. Furthermore, we also constructed co-expression networks from the entire transcriptome and found that ASD candidate genes were enriched in modules related to mitochondrial function, protein translation, and ubiquitination. Hub genes central to these ASD-enriched modules were further identified, and their functions supported these ontological find-ings. Overall, our multi-dimensional co-expression analysis of ASD candidate genes in the normal developing human brain suggests the heterogeneous set of ASD candidates share tran-scriptional networks related to synapse formation and elimina-tion, protein turnover, and mitochondrial function