Impact on the Risk and Severity of Childhood Onset Schizophrenia of Schizophrenia Risk Genetic Variants at the DRD2 and ZNF804A Loci

Алфимова, М. В.; Никитина, С. Г.; Лежейко, Т. В.; Nv, Simashkova; Голимбет, В. Е.

doi:10.1007/s10578-021-01245-z

Cited by 4 publications

(5 citation statements)

References 31 publications

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“…Interestingly, variants in DTNBP1 was also reported to show associations with the severity of negative symptoms ( Fanous et al, 2005 ; DeRosse et al, 2006 ). Some candidate-gene studies in this review may partially support the hypothesis ( Dubertret et al, 2001 ; Numata et al, 2007 ; Voisey et al, 2012 ; Alfimova et al, 2023 ) that some genes may be “pseudo-modifiers” for AAO. More future research is needed to clarify these speculations.…”

Section: Discussionmentioning

confidence: 61%

“…Another study genotyped 7 SNPs on the DRD2 gene, and found that the polymorphism rs2734839 was significantly associated with schizophrenia diagnosis and AAO, and schizophrenia patients carrying the GA genotype showed a later AAO than those carrying the AA genotype ( p = 0.012) ( Voisey et al, 2012 ). Another study compared childhood-onset schizophrenia (COS: AAO ranged from 3 to 16) and adult-onset schizophrenia (AOS: AAO ranged from 18 to 25) patients, and found that the frequency of DRD2 genotypes significantly differed in these two groups, with a lower frequency of risk allele C of SNP rs2514218 in the COS group ( Alfimova et al, 2023 ). Several other studies also tested SNPs in DRD2 , but did not report any positive findings ( Itokawa et al, 1993 ; Xiao et al, 2013 ; Michalczyk et al, 2020a ).…”

Section: Methodsmentioning

confidence: 99%

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The genetic basis of onset age in schizophrenia: evidence and models

Zhan

Sham

et al. 2023

Front. Genet.

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Schizophrenia is a heritable neurocognitive disorder affecting about 1% of the population, and usually has an onset age at around 21–25 in males and 25–30 in females. Recent advances in genetics have helped to identify many common and rare variants for the liability to schizophrenia. Earlier evidence appeared to suggest that younger onset age is associated with higher genetic liability to schizophrenia. Clinical longitudinal research also found that early and very-early onset schizophrenia are associated with poor clinical, neurocognitive, and functional profiles. A recent study reported a heritability of 0.33 for schizophrenia onset age, but the genetic basis of this trait in schizophrenia remains elusive. In the pre-Genome-Wide Association Study (GWAS) era, genetic loci found to be associated with onset age were seldom replicated. In the post-Genome-Wide Association Study era, new conceptual frameworks are needed to clarify the role of onset age in genetic research in schizophrenia, and to identify its genetic basis. In this review, we first discussed the potential of onset age as a characterizing/subtyping feature for psychosis, and as an important phenotypic dimension of schizophrenia. Second, we reviewed the methods, samples, findings and limitations of previous genetic research on onset age in schizophrenia. Third, we discussed a potential conceptual framework for studying the genetic basis of onset age, as well as the concepts of susceptibility, modifier, and “mixed” genes. Fourth, we discussed the limitations of this review. Lastly, we discussed the potential clinical implications for genetic research of onset age of schizophrenia, and how future research can unveil the potential mechanisms for this trait.

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Section: Discussionmentioning

confidence: 61%

Section: Methodsmentioning

confidence: 99%

The genetic basis of onset age in schizophrenia: evidence and models

Zhan

Sham

et al. 2023

Front. Genet.

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“…2.1 SNPs in SCZ risk genes affecting the dopaminergic system DRD2 has been shown to be an important player in the development of SCZ according to several studies (Yao et al, 2015;Benjamin et al, 2022;Alfimova et al, 2023). DRD2, which codes for the type-2 dopamine receptor (D2R) is an important G-coupled presynaptic receptor of the dopaminergic system (Oda et al, 2015).…”

Section: Genetic Complexity Of Sczmentioning

confidence: 99%

Implications of SNP-triggered miRNA dysregulation in Schizophrenia development

Mohamed,

Freude

2024

Front. Genet.

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This review examines the substantial involvement of Single Nucleotide Polymorphisms (SNPs) and microRNAs (miRNAs) in the etiology and susceptibility to Schizophrenia, with particular emphasis on the dopaminergic, glutamatergic, and GABAergic systems. It elucidates the potential of SNPs to disrupt miRNA-mRNA interactions, leading to alterations in the regulatory mechanisms of Schizophrenia risk genes and subsequently influencing the susceptibility to Schizophrenia. Specific attention is given to the impact of SNPs in DICER, DROSHA, and DGCR8, as well as the potential for changes in DRD2 gene expression driven by miR-9 and miR-326, heightening the likelihood of Schizophrenia development. Furthermore, the review explores genetic alterations in the glutamatergic system, focusing on modifications linked to GRIN2A and its associated miRNAs, which have been reported to have a notable impact on the occurrence of Schizophrenia. Knowledge of the involvement of SNPs within miRNAs in influencing the expression of essential genes within the GABA system are emerging and described in this review, including their potential consequences for Schizophrenia.

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“…ZNF804A has recently been cataloged, by means of GWASs, as a risk gene in schizophrenia [ 84 ], due to its importance in the regulation of COMT and serine protease 16 (PRSS16) gene expression [ 85 ]. The gene has also been associated with the ability to regulate DA levels, specifically, certain variations affect the ability to capture receptors [ 86 , 87 ].…”

Section: Geneticsmentioning

confidence: 99%

Genetic polymorphism and neuroanatomical changes in schizophrenia

Năstase

Vlaicu²,

Trifu³

2022

Rom J Morphol Embryol

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The article is a review of the latest meta-analyses regarding the genetic spectrum in schizophrenia, discussing the risks given by the disruptedin-schizophrenia 1 (DISC1), catechol-O-methyltransferase (COMT), monoamine oxidases-A/B (MAO-A/B), glutamic acid decarboxylase 67 (GAD67) and neuregulin 1 (NRG1) genes, and dysbindin-1 protein. The DISC1 polymorphism significantly increases the risk of schizophrenia, as well injuries from the prefrontal cortex that affect connectivity. NRG1 is one of the most important proteins involved. Its polymorphism is associated with the reduction of areas in the corpus callosum, right uncinate, inferior lateral fronto-occipital fascicle, right external capsule, fornix, right optic tract, gyrus. NRG1 and the ErbB4 receptor (tyrosine kinase receptor) are closely related to the N-methyl-D-aspartate receptor (NMDAR) (glutamate receptor). COMT is located on chromosome 22 and together with interleukin-10 (IL-10) have an anti-inflammatory and immunosuppressive function that influences the dopaminergic system. MAO gene methylation has been associated with mental disorders. MAO-A is a risk gene in the onset of schizophrenia, more precisely a certain type of single-nucleotide polymorphism (SNP), at the gene level, is associated with schizophrenia. In schizophrenia, we find deficits of the γ-aminobutyric acid (GABA)ergic neurotransmitter, the dysfunctions being found predominantly at the level of the substantia nigra. In schizophrenia, missing an allele at GAD67, caused by a SNP, has been correlated with decreases in parvalbumin (PV), somatostatin receptor (SSR), and GAD ribonucleic acid (RNA). Resulting in the inability to mature PV and SSR neurons, which has been associated with hyperactivity.

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Impact on the Risk and Severity of Childhood Onset Schizophrenia of Schizophrenia Risk Genetic Variants at the DRD2 and ZNF804A Loci

Cited by 4 publications

References 31 publications

The genetic basis of onset age in schizophrenia: evidence and models

The genetic basis of onset age in schizophrenia: evidence and models

Implications of SNP-triggered miRNA dysregulation in Schizophrenia development

Genetic polymorphism and neuroanatomical changes in schizophrenia

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