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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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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. |
format | Online Article Text |
id | pubmed-9710780 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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