Genome-wide, integrative analysis implicates microRNA dysregulation in autism spectrum disorder

Genetic variants conferring risk for autism spectrum disorder (ASD) have been identified, but the role of post-transcriptional mechanisms in ASD is not well understood. We performed genome-wide microRNA (miRNA) expression profiling in post-mortem brains from ASD patients and controls, and identified miRNAs and co-regulated modules perturbed in ASD. Putative targets of these ASD-affected miRNAs were enriched for genes previously implicated in ASD risk. We confirmed causal regulatory relationships between several miRNAs and their putative target mRNAs in primary human neural progenitors. These include hsa-miR-21-3p, a miRNA up-regulated in ASD of unknown CNS function, which targets neuronal genes down-regulated in ASD, and a novel, primate-specific miRNA down-regulated in ASD, hsa_can_1002-m, which regulates the EGFR and FGFR signaling pathways involved in neural development and immune function. Our findings support a role for miRNA dysregulation in ASD pathophysiology and provide a rich dataset and framework for future analyses of miRNAs in neuropsychiatric diseases.