4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-022-31053-5

Keywords

-

Funding

  1. Simons Foundation
  2. University of Maryland Brain and Tissue Bank component of the NIH NeuroBiobank
  3. NIMH [R01MH110927, U01MH115746, P50-MH106438, R01 MH-109912, R01 MH094714, MH102603, MH126481]
  4. SFARI Bridge to Independence Award [NIMH R01-MH121521, NIMH R01MH123922, NICHD-P50-HD103557]
  5. NINDS [NS106447, NS115821]
  6. NHGRI [HG011641]
  7. Simons Foundation (SFARI) [573689]
  8. James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition-Scholar Award [220020467]

Ask authors/readers for more resources

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.
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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available