Association between resting-state functional brain connectivity and gene expression is altered in autism spectrum disorder

Abstract

Gene expression covaries with brain activity as measured by resting state functional MRI. However, it is unclear how genomic differences driven by disease state can affect this relationship. Here, we integrate brain gene expression datasets of neurotypical controls and autistic (ASD) patients with regionally matched brain activity measurements from fMRI datasets. We identify genes linked with brain activity whose association is disrupted in ASD patients. We identified a subset of genes that showed a differential developmental trajectory in ASD patients compared with controls. These genes are enriched in voltage-gated ion channels and inhibitory neurons, pointing to excitation-inhibition imbalance in ASD. We further assessed differences at the regional level showing that the primary visual cortex is the most affected region in ASD patients. Our results link disrupted brain expression patterns of individuals with ASD to brain activity and show developmental, cell type, and regional enrichment of activity linked genes.