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

Gene expression covaries with brain activity as measured by resting state functional magnetic resonance imaging (MRI). However, it is unclear how genomic differences driven by disease state can affect this relationship. Here, we integrate from the ABIDE I and II imaging cohorts with datasets of gene expression in brains of neurotypical individuals and individuals with autism spectrum disorder (ASD) with regionally matched brain activity measurements from fMRI datasets. We identify genes linked with brain activity whose association is disrupted in ASD. We identified a subset of genes that showed a differential developmental trajectory in individuals with ASD 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. 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. Gene expression patterns have been associated with functional activity patterns in the brain. Here the authors determine how gene expression patterns in the human brain supports brain phenotypes obtained from resting state fMRI imaging, identifying brain regions and genes relevant to autism.

Automated summary

This study integrates gene expression data from brains of neurotypical individuals and individuals with autism spectrum disorder (ASD) with functional magnetic resonance imaging (fMRI) data to identify disrupted brain expression patterns in individuals with ASD, particularly genes associated with voltage-gated ion channels and inhibitory neurons. The research also highlights differences in the developmental trajectory of certain genes in individuals with ASD compared to controls, and shows that the primary visual cortex is the most affected region in ASD.