Molecular signatures from multi‐omics of autism spectrum disorders and schizophrenia

• Published in: Journal of neurochemistry Vol. 159; no. 4; pp. 647 - 659
• Main Authors: Nomura, Jun, Mardo, Matthew, Takumi, Toru
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2021
• Subjects: Animals; Autism; autism spectrum disorder; Autism Spectrum Disorder - genetics; Bioinformatics; Chromosomes; Copy number; Disorders; enrichment analysis; Etiology; gene ontology; Genes; Genetic Predisposition to Disease; Genomics; Heterogeneity; Humans; Mental disorders; Metabolic Networks and Pathways - genetics; neurodevelopmental disorder; Neurodevelopmental disorders; Proteins; protein–protein interaction network; Schizophrenia; Schizophrenia - genetics; Social factors; gene ontology; protein-protein interaction network; schizophrenia; autism spectrum disorder; neurodevelopmental disorder; enrichment analysis
• DOI: 10.1111/jnc.15514
• ISSN: 0022-3042

The genetic and phenotypic heterogeneity of autism spectrum disorder (ASD) impedes the unification of multiple biological hypotheses in an attempt to explain the complex features of ASD, such as impaired social communication, social interaction deficits, and restricted and repetitive patterns of behavior. However, recent psychiatric genetic studies have identified numerous risk genes and chromosome loci (copy number variation: CNV) which enable us to analyze at the single gene level and utilize system‐level approaches. In this review, we focus on ASD as a major neurodevelopmental disorder and review recent findings mainly from the bioinformatics of omics studies. Additionally, by comparing these data with other major psychiatric disorders, including schizophrenia (SCZ), we identify unique characteristics of both diseases from multiple enrichment, pathway, and protein–protein interaction networks (PPIs) analyses using susceptible genes found in recent large‐scale genetic studies. These unified, systematic approaches highlight unique characteristics of both disorders from multiple aspects and demonstrate how convergent pathways can contribute to an understanding of the complex etiology of such neurodevelopmental and neuropsychiatric disorders. The genetic and clinical heterogeneity of autism spectrum disorder (ASD) and schizophrenia (SCZ) perturb unifying possible biological hypotheses to tackle these disorders. However, recent large‐scale human genetic studies and genome‐wide omics analysis enable us to perform multi‐omic system‐level analysis. We highlight the achievements of recent omics studies and emphasize how the multi‐omics approach is suitable to sort out the complex etiology of these disorders. In addition, we show unique characteristics of these disorders as well as convergent pathways and core networks. We also discuss limitations and future perspectives of the method toward understanding the pathophysiology of these disorders.