
Autism spectrum disorders (ASDs) are highly heritable, and six genome-wide association studies (GWASs) of ASDs have been published to date. In this study, we have integrated the findings from these GWASs with other genetic data to identify enriched genetic networks that are associated with ASDs. We conducted bioinformatics and systematic literature analyses of 200 top-ranked ASD candidate genes from five published GWASs. The sixth GWAS was used for replication and validation of our findings. Further corroborating evidence was obtained through rare genetic variant studies, that is, exome sequencing and copy number variation (CNV) studies, and/or other genetic evidence, including candidate gene association, microRNA and gene expression, gene function and genetic animal studies. We found three signaling networks regulating steroidogenesis, neurite outgrowth and (glutamatergic) synaptic function to be enriched in the data. Most genes from the five GWASs were also implicated--independent of gene size--in ASDs by at least one other line of genomic evidence. Importantly, A-kinase anchor proteins (AKAPs) functionally integrate signaling cascades within and between these networks. The three identified protein networks provide an important contribution to increasing our understanding of the molecular basis of ASDs. In addition, our results point towards the AKAPs as promising targets for developing novel ASD treatments.
Male, Molecular Animal Physiology, A Kinase Anchor Proteins, Genes, Child Development Disorders, Pervasive, DCN 3: Neuroinformatics, Humans, Original Article, Female, Genetic Predisposition to Disease, DCN PAC - Perception action and control NCEBP 9 - Mental health, DCN PAC - Perception action and control IGMD 3: Genomic disorders and inherited multi-system disorders, IGMD 3: Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory, Child, Genome-Wide Association Study
Male, Molecular Animal Physiology, A Kinase Anchor Proteins, Genes, Child Development Disorders, Pervasive, DCN 3: Neuroinformatics, Humans, Original Article, Female, Genetic Predisposition to Disease, DCN PAC - Perception action and control NCEBP 9 - Mental health, DCN PAC - Perception action and control IGMD 3: Genomic disorders and inherited multi-system disorders, IGMD 3: Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory, Child, Genome-Wide Association Study
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