Currently recognized genes for schizophrenia: High‐resolution chromosome ideogram representation

Abstract

A large body of genetic data from schizophrenia-related research has identified an assortment of genes and disturbed pathways supporting involvement of complex genetic components for schizophrenia spectrum and other psychotic disorders. Advances in genetic technology and expanding studies with searchable genomic databases have led to multiple published reports, allowing us to compile a master list of known, clinically relevant, or susceptibility genes contributing to schizophrenia. We searched key words related to schizophrenia and genetics from peer-reviewed medical literature sources, authoritative public access psychiatric websites and genomic databases dedicated to gene discovery and characterization of schizophrenia. Our list of 560 genes were arranged in alphabetical order in tabular form with gene symbols placed on high-resolution human chromosome ideograms. Genome wide pathway analysis using GeneAnalytics was carried out on the resulting list of genes to assess the underlying genetic architecture for schizophrenia. Recognized genes of clinical relevance, susceptibility or causation impact a broad range of biological pathways and mechanisms including ion channels (e.g., CACNA1B, CACNA1C, CACNA1H), metabolism (e.g., CYP1A2, CYP2C19, CYP2D6), multiple targets of neurotransmitter pathways impacting dopamine, GABA, glutamate, and serotonin function, brain development (e.g., NRG1, RELN), signaling peptides (e.g., PIK3CA, PIK4CA) and immune function (e.g., HLA-DRB1, HLA-DQA1) and interleukins (e.g., IL1A, IL10, IL6). This summary will enable clinical and laboratory geneticists, genetic counselors, and other clinicians to access convenient pictorial images of the distribution and location of contributing genes to inform diagnosis and gene-based treatment as well as provide risk estimates for genetic counseling of families with affected relatives.

Genome-Wide Transcriptional Profiling and Structural Magnetic Resonance Imaging in the Maternal Immune Activation Model of Neurodevelopmental Disorders

“…In particular, when comparing our results with the currently recognized risk genes for schizophrenia, 5 of the affected genes in the mPFC (ADORA2A, CNP, DRD2, MAG, PPP1RB1), and 21 of the affected genes in the NAc (APOD, CACNA 1B, DRD3, FOXP2, GLS, GRIN2A, HIST1H2BC, HRT1A, HRT2A, HRT4, MAG, MGST1, MYO16, OXT, PBRM1, PDYN, ST3GAL1, SULT4A1, TSNAX, VAMP4) fall into this list (Butler et al 2016). In agreement with previous reports by Connor et al (2012) and Smith et al (2007), prenatal immune activation leads to less extensive gene expression changes in the mPFC (n = 116 genes) as compared to the NAc (n = 251 genes) (Smith et al 2007;Connor et al 2012).…”

“…Of the 116 genes that were differentially expressed in the mPFC, 55 were downregulated and 61 were upregulated (Tables 1 and 2), while in the NAc, 126 were downregulated and 125 upregulated (Tables 3 and 4). Interestingly, many of these have been already associated with schizophrenia, such as adenosine 2a receptor (ADORA2a), apolipoprotein D (APOD), the dopamine receptors DRD2 and DRD3, forkhead box P2 (FOXP2), glutaminase (GLS), the glutamate receptor subunit GRIN2A, histone cluster 1 (HIST1H2BC), 5-hydroxytryptamine receptors (HTR1A, HTR2A, HTR4), oxytocin (OXT), solute carriers (SLC17A7), and, among others, vescicle-associated membrane protein 4 (VAMP4) (Butler et al 2016). A Gene Ontology (GO) enrichment analysis computing the DEGs in the mPFC and NAc is presented in Supplementary Table 2.…”

GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia

“…The original gene lists reported in the literature included 792 genes for ASD [21], 290 genes for bipolar disorder [22] and 560 genes for schizophrenia [23], and of these, 23 genes were found in common in all three conditions (see Table 1). Functional analysis of the 23 genes identified from the submitted list of genes showed a high match for schizophrenia (17 genes, score = 15.1) with medium-match scores representing 25 other disorders including bipolar disorder (nine genes, score = 9.6) and autism spectrum disorder (10 genes, score = 9.1).…”

“…We used recently published list of genes found to be clinically relevant and known to play a role in ASD [21], bipolar disorder [22] and schizophrenia [23] for molecular profiling and pathway analysis of genes common to all three neuropsychiatric conditions with similar features. GeneAnalytics (…”

“…Herein, we use the GeneAnalytics [20] program pathway analysis to further profile and characterize the underlying molecular architecture of clinically and etiologically relevant genes common to ASD [21], bipolar disorder [22] and schizophrenia [23] and associated diseases.…”