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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.

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


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

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