Format

Send to

Choose Destination
Nat Neurosci. 2016 Nov;19(11):1454-1462. doi: 10.1038/nn.4353. Epub 2016 Aug 1.

Genome-wide prediction and functional characterization of the genetic basis of autism spectrum disorder.

Author information

1
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
2
Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
3
Department of Computer Science, Princeton University, Princeton, New Jersey, USA.
4
Simons Foundation, New York, New York, USA.
5
Flatiron Institute, Simons Foundation, New York, New York, USA.

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic basis. Yet, only a small fraction of potentially causal genes-about 65 genes out of an estimated several hundred-are known with strong genetic evidence from sequencing studies. We developed a complementary machine-learning approach based on a human brain-specific gene network to present a genome-wide prediction of autism risk genes, including hundreds of candidates for which there is minimal or no prior genetic evidence. Our approach was validated in a large independent case-control sequencing study. Leveraging these genome-wide predictions and the brain-specific network, we demonstrated that the large set of ASD genes converges on a smaller number of key pathways and developmental stages of the brain. Finally, we identified likely pathogenic genes within frequent autism-associated copy-number variants and proposed genes and pathways that are likely mediators of ASD across multiple copy-number variants. All predictions and functional insights are available at http://asd.princeton.edu.

PMID:
27479844
PMCID:
PMC5803797
DOI:
10.1038/nn.4353
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center