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GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia
Naveen S. Khanzada 1
Received: 18 January 2017 / Accepted: 23 February 2017 / Published: 28 February 2017
Abstract
:
Bipolar disorder (BPD) and schizophrenia (SCH) show similar neuropsychiatric behavioral disturbances, including impaired social interaction and communication, seen in autism spectrum disorder (ASD) with multiple overlapping genetic and environmental influences implicated in risk and course of illness. GeneAnalytics software was used for pathway analysis and genetic profiling to characterize common susceptibility genes obtained from published lists for ASD (792 genes), BPD (290 genes) and SCH (560 genes). Rank scores were derived from the number and nature of overlapping genes, gene-disease association, tissue specificity and gene functions subdivided into categories (e.g., diseases, tissues or functional pathways). Twenty-three genes were common to all three disorders and mapped to nine biological
Superpathways including Circadian entrainment (10 genes, score = 37.0), Amphetamine addiction (five genes, score = 24.2), and Sudden infant death syndrome (six genes, score = 24.1). Brain tissues included the medulla oblongata (11 genes, score = 2.1), thalamus (10 genes, score = 2.0) and hypothalamus (nine genes, score = 2.0) with six common genes (BDNF, DRD2, CHRNA7, HTR2A, SLC6A3, and TPH2).
Overlapping genes impacted dopamine and serotonin homeostasis and signal transduction pathways, impacting mood, behavior and physical activity level. Converging effects on pathways governing circadian rhythms support a core etiological relationship between neuropsychiatric illnesses and sleep disruption with hypoxia and central brain stem dysfunction.
The genetic architecture of schizophrenia, bipolar disorder, obsessive-compulsive disorder and autism spectrum disorder
2018
Abstract
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.
Naveen S. Khanzada 1
Received: 18 January 2017 / Accepted: 23 February 2017 / Published: 28 February 2017
Abstract
:
Bipolar disorder (BPD) and schizophrenia (SCH) show similar neuropsychiatric behavioral disturbances, including impaired social interaction and communication, seen in autism spectrum disorder (ASD) with multiple overlapping genetic and environmental influences implicated in risk and course of illness. GeneAnalytics software was used for pathway analysis and genetic profiling to characterize common susceptibility genes obtained from published lists for ASD (792 genes), BPD (290 genes) and SCH (560 genes). Rank scores were derived from the number and nature of overlapping genes, gene-disease association, tissue specificity and gene functions subdivided into categories (e.g., diseases, tissues or functional pathways). Twenty-three genes were common to all three disorders and mapped to nine biological
Superpathways including Circadian entrainment (10 genes, score = 37.0), Amphetamine addiction (five genes, score = 24.2), and Sudden infant death syndrome (six genes, score = 24.1). Brain tissues included the medulla oblongata (11 genes, score = 2.1), thalamus (10 genes, score = 2.0) and hypothalamus (nine genes, score = 2.0) with six common genes (BDNF, DRD2, CHRNA7, HTR2A, SLC6A3, and TPH2).
Overlapping genes impacted dopamine and serotonin homeostasis and signal transduction pathways, impacting mood, behavior and physical activity level. Converging effects on pathways governing circadian rhythms support a core etiological relationship between neuropsychiatric illnesses and sleep disruption with hypoxia and central brain stem dysfunction.
The genetic architecture of schizophrenia, bipolar disorder, obsessive-compulsive disorder and autism spectrum disorder
2018
Abstract
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.
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