title: Genome-wide prediction and functional characterization of the genetic basis of autism spectrum disorder.
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.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
authors.forename: Arjun
authors.identifier: 0000-0002-7980-4110
authors.initials: A
authors.lastname: Krishnan
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
authors.forename: Ran
authors.identifier: 0000-0002-7630-1251
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Computer Science, Princeton University, Princeton, New Jersey, USA.
authors.forename: Victoria
authors.identifier: 0000-0002-3201-9983
authors.initials: V
authors.lastname: Yao
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
authors.forename: Chandra L
authors.initials: CL
authors.lastname: Theesfeld
authors.affiliation: Simons Foundation, New York, New York, USA.
authors.forename: Aaron K
authors.identifier: 0000-0002-7294-0646
authors.initials: AK
authors.lastname: Wong
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
authors.forename: Alicja
authors.initials: A
authors.lastname: Tadych
authors.affiliation: Simons Foundation, New York, New York, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Volfovsky
authors.affiliation: Simons Foundation, New York, New York, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Packer
authors.affiliation: Simons Foundation, New York, New York, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Lash
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.|Department of Computer Science, Princeton University, Princeton, New Jersey, USA.|Flatiron Institute, Simons Foundation, New York, New York, USA.
authors.forename: Olga G
authors.initials: OG
authors.lastname: Troyanskaya
mesh_terms: D000067877:Autism Spectrum Disorder / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*