Dataset Information

Glial changes in schizophrenia: Genetic and epigenetic approach.

ABSTRACT:

Background

Schizophrenia (SCZ) is a severe mental illness that affects one percent of the population, affecting how people think, feel, and behave. Evidence suggests glial cell alteration and some researchers have found genetic risk loci and epigenetic marks that may regulate glia-related genes implicated in SCZ.

Aim

The aim of this study is to identify genetic and epigenetic changes that have been reported in glial cells or glial-associated genes in SCZ.

Materials and methods

We searched the articles from PubMed, PubMed Central, Medline, Medscape, and Embase databases up to December 2020 to identify relevant peer-reviewed articles in English. The titles and abstracts were screened to eliminate irrelevant citations.

Results

Twenty-four original articles were included in the review. Studies were categorized into the following four thematic via: (1) oligodendrocytes, (2) microglia, (3) astrocytes, and (4) perspectives.

Conclusion

This study is the first of its kind to review research on genetic variants and epigenetic modifications associated with glia-related genes implicated in SCZ. Epigenetic evidence is considerably less than genetic evidence in this field. Understanding the pathways of some risk genes and their genetic and epigenetic regulation allows us to understand and find potential targets for future interventions in this mental illness.

SUBMITTER: Francisco RD

PROVIDER: S-EPMC8992743 | biostudies-literature | 2022 Jan-Feb

REPOSITORIES: biostudies-literature

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Publications

Glial changes in schizophrenia: Genetic and epigenetic approach.

Francisco Ramos Daniel RD Fernando Vazquez V Norma Estrada E Madai Méndez Edna ME Marcelo Barraza B

Indian journal of psychiatry 20220121 1

<h4>Background</h4>Schizophrenia (SCZ) is a severe mental illness that affects one percent of the population, affecting how people think, feel, and behave. Evidence suggests glial cell alteration and some researchers have found genetic risk loci and epigenetic marks that may regulate glia-related genes implicated in SCZ.<h4>Aim</h4>The aim of this study is to identify genetic and epigenetic changes that have been reported in glial cells or glial-associated genes in SCZ.<h4>Materials and methods< ...[more]

PMID: 35400734

Similar Datasets

Project description:BackgroundOne of the major challenges in current psychiatric epigenetic studies is the tissue specificity of epigenetic changes since access to brain samples is limited. Peripheral tissues have been studied as surrogates but the knowledge of cross-tissue genetic-epigenetic characteristics remains largely unknown. In this work, we conducted a comprehensive investigation of genetic influence on DNA methylation across brain and peripheral tissues with the aim to characterize cross-tissue genetic-epigenetic effects and their roles in the pathophysiology of psychiatric disorders.MethodsGenome-wide methylation quantitative trait loci (meQTLs) from brain prefrontal cortex, whole blood, and saliva were identified separately and compared. Focusing on cis-acting effects, we tested the enrichment of cross-tissue meQTLs among cross-tissue expression QTLs and genetic risk loci of various diseases, including major psychiatric disorders. CpGs targeted by cross-tissue meQTLs were also tested for genomic distribution and functional enrichment as well as their contribution to methylation correlation across tissues. Finally, a consensus co-methylation network analysis on the cross-tissue meQTL targeted CpGs was performed on data of the three tissues collected from schizophrenia patients and controls.ResultsWe found a significant overlap of cis meQTLs (45-73 %) and targeted CpG sites (31-68 %) among tissues. The majority of cross-tissue meQTLs showed consistent signs of cis-acting effects across tissues. They were significantly enriched in genetic risk loci of various diseases, especially schizophrenia, and also enriched in cross-tissue expression QTLs. Compared to CpG sites not targeted by any meQTLs, cross-tissue targeted CpGs were more distributed in CpG island shores and enhancer regions, and more likely had strong correlation with methylation levels across tissues. The targeted CpGs were also annotated to genes enriched in multiple psychiatric disorders and neurodevelopment-related pathways. Finally, we identified one co-methylation network shared between brain and blood showing significant schizophrenia association (p = 5.5 × 10-6).ConclusionsOur results demonstrate prevalent cross-tissue meQTL effects and their contribution to the correlation of CpG methylation across tissues, while at the same time a large portion of meQTLs show tissue-specific characteristics, especially in brain. Significant enrichment of cross-tissue meQTLs in expression QTLs and genetic risk loci of schizophrenia suggests the potential of these cross-tissue meQTLs for studying the genetic effect on schizophrenia. The study provides compelling motivation for a well-designed experiment to further validate the use of surrogate tissues in the study of psychiatric disorders.

Project description:BackgroundThe quest to understand the neurobiology of schizophrenia and bipolar disorder is ongoing with multiple lines of evidence indicating abnormalities of glia, mitochondria, and glutamate in both disorders. Despite high heritability estimates of 81% for schizophrenia and 75% for bipolar disorder, compelling links between findings from neurobiological studies, and findings from large-scale genetic analyses, are only beginning to emerge.MethodTen publically available gene sets (pathways) related to glia, mitochondria, and glutamate were tested for association to schizophrenia and bipolar disorder using MAGENTA as the primary analysis method. To determine the robustness of associations, secondary analyses were performed with: ALIGATOR, INRICH, and Set Screen. Data from the Psychiatric Genomics Consortium (PGC) were used for all analyses. There were 1,068,286 SNP-level p-values for schizophrenia (9,394 cases/12,462 controls), and 2,088,878 SNP-level p-values for bipolar disorder (7,481 cases/9,250 controls).ResultsThe Glia-Oligodendrocyte pathway was associated with schizophrenia, after correction for multiple tests, according to primary analysis (MAGENTA p = 0.0005, 75% requirement for individual gene significance) and also achieved nominal levels of significance with INRICH (p = 0.0057) and ALIGATOR (p = 0.022). For bipolar disorder, Set Screen yielded nominally and method-wide significant associations to all three glial pathways, with strongest association to the Glia-Astrocyte pathway (p = 0.002).ConclusionsConsistent with findings of white matter abnormalities in schizophrenia by other methods of study, the Glia-Oligodendrocyte pathway was associated with schizophrenia in our genomic study. These findings suggest that the abnormalities of myelination observed in schizophrenia are at least in part due to inherited factors, contrasted with the alternative of purely environmental causes (e.g. medication effects or lifestyle). While not the primary purpose of our study, our results also highlight the consequential nature of alternative choices regarding pathway analysis, in that results varied somewhat across methods, despite application to identical datasets and pathways.

Dataset Information

Glial changes in schizophrenia: Genetic and epigenetic approach.

Background

Aim

Materials and methods

Results

Conclusion

Publications

Glial changes in schizophrenia: Genetic and epigenetic approach.

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