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Maternal immune activation induces methylation changes in schizophrenia genes

Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could contribute to adult-onset schizophrenia. In this...

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Detalles Bibliográficos
Autores principales: Johnson, Thomas, Saatci, Defne, Handunnetthi, Lahiru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710780/
https://www.ncbi.nlm.nih.gov/pubmed/36449485
http://dx.doi.org/10.1371/journal.pone.0278155
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author Johnson, Thomas
Saatci, Defne
Handunnetthi, Lahiru
author_facet Johnson, Thomas
Saatci, Defne
Handunnetthi, Lahiru
author_sort Johnson, Thomas
collection PubMed
description Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could contribute to adult-onset schizophrenia. In this study, we investigated if maternal immune activation induces changes in methylation of genes linked to schizophrenia. We found that differentially expressed genes in schizophrenia brain were significantly enriched among MIA induced differentially methylated genes in the foetal brain in a cell-type-specific manner. Upregulated genes in layer V pyramidal neurons were enriched among hypomethylated genes at gestational day 9 (fold change = 1.57, FDR = 0.049) and gestational day 17 (fold change = 1.97, FDR = 0.0006). A linear regression analysis, which showed a decrease in gene expression with an increase in methylation in gestational day 17, supported findings from our enrichment analysis. Collectively, our results highlight a connection between MIA driven methylation changes during gestation and schizophrenia gene expression signatures in the adult brain. These findings carry important implications for early preventative strategies in schizophrenia.
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spelling pubmed-97107802022-12-01 Maternal immune activation induces methylation changes in schizophrenia genes Johnson, Thomas Saatci, Defne Handunnetthi, Lahiru PLoS One Research Article Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could contribute to adult-onset schizophrenia. In this study, we investigated if maternal immune activation induces changes in methylation of genes linked to schizophrenia. We found that differentially expressed genes in schizophrenia brain were significantly enriched among MIA induced differentially methylated genes in the foetal brain in a cell-type-specific manner. Upregulated genes in layer V pyramidal neurons were enriched among hypomethylated genes at gestational day 9 (fold change = 1.57, FDR = 0.049) and gestational day 17 (fold change = 1.97, FDR = 0.0006). A linear regression analysis, which showed a decrease in gene expression with an increase in methylation in gestational day 17, supported findings from our enrichment analysis. Collectively, our results highlight a connection between MIA driven methylation changes during gestation and schizophrenia gene expression signatures in the adult brain. These findings carry important implications for early preventative strategies in schizophrenia. Public Library of Science 2022-11-30 /pmc/articles/PMC9710780/ /pubmed/36449485 http://dx.doi.org/10.1371/journal.pone.0278155 Text en © 2022 Johnson et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Johnson, Thomas
Saatci, Defne
Handunnetthi, Lahiru
Maternal immune activation induces methylation changes in schizophrenia genes
title Maternal immune activation induces methylation changes in schizophrenia genes
title_full Maternal immune activation induces methylation changes in schizophrenia genes
title_fullStr Maternal immune activation induces methylation changes in schizophrenia genes
title_full_unstemmed Maternal immune activation induces methylation changes in schizophrenia genes
title_short Maternal immune activation induces methylation changes in schizophrenia genes
title_sort maternal immune activation induces methylation changes in schizophrenia genes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710780/
https://www.ncbi.nlm.nih.gov/pubmed/36449485
http://dx.doi.org/10.1371/journal.pone.0278155
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