Integrative gene network analysis provides novel regulatory relationships, genetic contributions and susceptible targets in autism spectrum disorders.
Autism spectrum disorders (ASDs) are a group of diseases exhibiting impairment in social drive, communication/language skills and stereotyped behaviors. Though an increased number of candidate genes and molecular interactions have been identified by various approaches, the pathogenesis remains elusive. Based on clinical observations, data from accessible GWAS and expression datasets we identified ASDs gene candidates. Integrative gene network and a novel CNV-centric Node Network (CNN) analysis method highlighted ASDs-associated key elements and biological processes. Functional analysis identified neurological functions including synaptic cholinergic receptor (CHRNA) families, dopamine receptor (DRD2), and correlations between social behavior and oxytocin related pathways. CNN analysis of genome-wide genetic and expression data identified inheritance-related clusters related to PTEN/TSC1/FMR1 and mTor/PI3K regulation. Integrative analysis identified potential regulators of networks, specifically TNF and beta-estradiol, suggesting a potential central role in ASDs. Our data provide information on potential disease mechanisms, and key regulators that may generate novel postulations, and diagnostic molecular biomarkers.
Laboratory of Clinical and Developmental Genomics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. leetl@mail.nih.gov
Tin-Lap
TL
Lee
Margarita J
MJ
Raygada
Owen M
OM
Rennert
D015415:Biomarkers; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D008297:Male; D008957:Models, Genetic; D010121:Oxytocin / Q000378:metabolism; D011110:Polymorphism, Genetic; D011950:Receptors, Cholinergic / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D015415:Biomarkers; D011950:Receptors, Cholinergic; D017448:Receptors, Dopamine D2; D010121:Oxytocin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases