title: Neurodevelopmental and neuropsychiatric disorders represent an interconnected molecular system.
abstract: Many putative genetic factors that confer risk to neurodevelopmental disorders such as autism spectrum disorders (ASDs) and X-linked intellectual disability (XLID), and to neuropsychiatric disorders including attention deficit hyperactivity disorder (ADHD) and schizophrenia (SZ) have been identified in individuals from diverse human populations. Although there is significant aetiological heterogeneity within and between these conditions, recent data show that genetic factors contribute to their comorbidity. Many studies have identified candidate gene associations for these mental health disorders, albeit this is often done in a piecemeal fashion with little regard to the inherent molecular complexity. Here, we sought to abstract relationships from our knowledge of systems level biology to help understand the unique and common genetic drivers of these conditions. We undertook a global and systematic approach to build and integrate available data in gene networks associated with ASDs, XLID, ADHD and SZ. Complex network concepts and computational methods were used to investigate whether candidate genes associated with these conditions were related through mechanisms of gene regulation, functional protein-protein interactions, transcription factor (TF) and microRNA (miRNA) binding sites. Although our analyses show that genetic variations associated with the four disorders can occur in the same molecular pathways and functional domains, including synaptic transmission, there are patterns of variation that define significant differences between disorders. Of particular interest is DNA variations located in intergenic regions that comprise regulatory sites for TFs or miRNA. Our approach provides a hypothetical framework, which will help discovery and analysis of candidate genes associated with neurodevelopmental and neuropsychiatric disorders.
authors: Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors: A S
authors: AS
authors: Cristino
authors: Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors: S M
authors: SM
authors: Williams
authors: 1] Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia [2] School of Psychology and Psychiatry, Monash University, Melbourne, VIC, Australia.
authors: Z
authors: Z
authors: Hawi
authors: Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors: J-Y
authors: JY
authors: An
authors: 1] Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia [2] School of Psychology and Psychiatry, Monash University, Melbourne, VIC, Australia.
authors: M A
authors: MA
authors: Bellgrove
authors: Greenwood Genetic Center, Greenwood, SC, USA.
authors: C E
authors: CE
authors: Schwartz
authors: Instituto de Física de São Carlos, Universidade de São Paulo, São Paulo, Brazil.
authors: L da F
authors: Lda F
authors: Costa
authors: Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors: C
authors: C
authors: Claudianos
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D030541:Databases, Genetic; D005786:Gene Expression Regulation / Q000235:genetics; D056726:Genetic Association Studies / Q000706:statistics & numerical data; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics; D008957:Models, Genetic; D012559:Schizophrenia / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D035683:MicroRNAs; D014157:Transcription Factors