The genetic architecture of schizophrenia, bipolar disorder, obsessive-compulsive disorder and autism spectrum disorder.

Journal: Molecular and cellular neurosciences

Volume: 88

Issue: 

Year of Publication: 2019

Affiliated Institutions:  System Genetics Working Group, Department of Genetics, Stellenbosch University, Stellenbosch, South Africa; Department of Genetics, Stellenbosch University, Stellenbosch, South Africa. System Genetics Working Group, Department of Genetics, Stellenbosch University, Stellenbosch, South Africa; Department of Genetics, Stellenbosch University, Stellenbosch, South Africa. Electronic address: nwm@sun.ac.za. SU/UCT MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Tygerberg, South Africa. Department of Psychiatry, Stellenbosch University, Tygerberg, South Africa. Department of Genetics, Stellenbosch University, Stellenbosch, South Africa.

Abstract summary 

Considerable evidence suggests that autism spectrum disorders (ASD), schizophrenia (SCZ), bipolar disorder (BD) and obsessive-compulsive disorder (OCD) share a common molecular aetiology, despite their unique clinical diagnostic criteria. The aim of this study was therefore to determine and characterise the common and unique molecular architecture of ASD, SCZ, BD and OCD. Gene lists were obtained from previously published studies for ASD, BD, SCZ and for OCD. Genes identified to be common to all disorders, or unique to one specific disorder, were included for enrichment analyses using the web-server tool Enrichr. Ten genes were identified to be commonly associated with the aetiology of ASD, SCZ, BD and OCD. Enrichment analyses determined that these genes are predominantly involved in the dopaminergic and serotonergic pathways, the voltage-gated calcium ion channel gene network, folate metabolism, regulation of the hippo signaling pathway, and the regulation of gene silencing and expression. In addition to well-characterised and previously described pathways, regulation of the hippo signaling pathway was commonly associated with ASD, SCZ, BD and OCD, implicating neural development and neuronal maintenance as key in neuropsychiatric disorders. In contrast, a large number of previously associated genes were shown to be disorder-specific. And unique disorder-specific pathways and biological processes were presented for ASD, BD, SCZ and OCD aetiology. Considering the current global incidence and prevalence rates of mental health disorders, focus should be placed on cross-disorder commonalities in order to realise actionable and translatable results to combat mental health disorders.

Authors & Co-authors:  O'Connell Kevin S KS McGregor Nathaniel W NW Lochner Christine C Emsley Robin R Warnich Louise L

Study Outcome 

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Statistics
Citations : 
Authors :  5
Identifiers
Doi : 10.1016/j.mcn.2018.02.010
SSN : 1095-9327
Study Population
Male,Female
Mesh Terms
Autism Spectrum Disorder
Other Terms
Genetic profiling;Mental illness;Molecular pathway analysis;Psychiatric genetics
Study Design
Cross Sectional Study
Study Approach
Country of Study
Publication Country
United States