Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/205773 |
Resumo: | Background: Psychiatric symptomatology during late childhood and early adolescence tends to persist later in life. In the present longitudinal study, we aimed to identify changes in genome-wide DNA methylation patterns that were associated with the emergence of psychopathology in youths from the Brazilian High-Risk Cohort (HRC) for psychiatric disorders. Moreover, for the differentially methylated genes, we verified whether differences in DNA methylation corresponded to differences in mRNA transcript levels by analyzing the gene expression levels in the blood and by correlating the variation of DNA methylation values with the variation of mRNA levels of the same individuals. Finally, we examined whether the variations in DNA methylation and mRNA levels were correlated with psychopathology measurements over time. Methods: We selected 24 youths from the HRC who presented with an increase in dimensional psychopathology at a 3-year follow-up as measured by the Child Behavior Checklist (CBCL). The DNA methylation and gene expression data were compared in peripheral blood samples (n = 48) obtained from the 24 youths before and after developing psychopathology. We implemented a methodological framework to reduce the effect of chronological age on DNA methylation using an independent population of 140 youths and the effect of puberty using data from the literature. Results: We identified 663 differentially methylated positions (DMPs) and 90 differentially methylated regions (DMRs) associated with the emergence of psychopathology. We observed that 15 DMPs were mapped to genes that were differentially expressed in the blood; among these, we found a correlation between the DNA methylation and mRNA levels of RB1CC1 and a correlation between the CBCL and mRNA levels of KMT2E. Of the DMRs, three genes were differentially expressed: ASCL2, which is involved in neurogenesis; HLA-E, which is mapped to the MHC loci; and RPS6KB1, the gene expression of which was correlated with an increase in the CBCL between the time points. Conclusions: We observed that changes in DNA methylation and, consequently, in gene expression in the peripheral blood occurred concurrently with the emergence of dimensional psychopathology in youths. Therefore, epigenomic modulations might be involved in the regulation of an individual’s development of psychopathology. |
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Spíndola, Letícia Maria NeryBelangero, Síntia Iole NogueiraRohde, Luis Augusto PaimSalum Junior, Giovanni Abrahão2020-02-13T04:21:31Z20191868-7083http://hdl.handle.net/10183/205773001110953Background: Psychiatric symptomatology during late childhood and early adolescence tends to persist later in life. In the present longitudinal study, we aimed to identify changes in genome-wide DNA methylation patterns that were associated with the emergence of psychopathology in youths from the Brazilian High-Risk Cohort (HRC) for psychiatric disorders. Moreover, for the differentially methylated genes, we verified whether differences in DNA methylation corresponded to differences in mRNA transcript levels by analyzing the gene expression levels in the blood and by correlating the variation of DNA methylation values with the variation of mRNA levels of the same individuals. Finally, we examined whether the variations in DNA methylation and mRNA levels were correlated with psychopathology measurements over time. Methods: We selected 24 youths from the HRC who presented with an increase in dimensional psychopathology at a 3-year follow-up as measured by the Child Behavior Checklist (CBCL). The DNA methylation and gene expression data were compared in peripheral blood samples (n = 48) obtained from the 24 youths before and after developing psychopathology. We implemented a methodological framework to reduce the effect of chronological age on DNA methylation using an independent population of 140 youths and the effect of puberty using data from the literature. Results: We identified 663 differentially methylated positions (DMPs) and 90 differentially methylated regions (DMRs) associated with the emergence of psychopathology. We observed that 15 DMPs were mapped to genes that were differentially expressed in the blood; among these, we found a correlation between the DNA methylation and mRNA levels of RB1CC1 and a correlation between the CBCL and mRNA levels of KMT2E. Of the DMRs, three genes were differentially expressed: ASCL2, which is involved in neurogenesis; HLA-E, which is mapped to the MHC loci; and RPS6KB1, the gene expression of which was correlated with an increase in the CBCL between the time points. Conclusions: We observed that changes in DNA methylation and, consequently, in gene expression in the peripheral blood occurred concurrently with the emergence of dimensional psychopathology in youths. Therefore, epigenomic modulations might be involved in the regulation of an individual’s development of psychopathology.application/pdfengClinical epigenetics. London. vol. 11 (2019), 146, 16 f.Transtornos mentaisEpigenômicaExpressão gênicaMetilaçãoTranscrição genéticaMental disordersEpigeneticsMethylationGene expressionTranscriptionDetecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youthsEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001110953.pdf.txt001110953.pdf.txtExtracted Texttext/plain81120http://www.lume.ufrgs.br/bitstream/10183/205773/2/001110953.pdf.txt6fb4dbe140d5ee5d3d05eb04a2c47056MD52ORIGINAL001110953.pdfTexto completo (inglês)application/pdf1478087http://www.lume.ufrgs.br/bitstream/10183/205773/1/001110953.pdf6f93a338e33621d6718f62ac3327af41MD5110183/2057732020-02-14 05:15:46.663758oai:www.lume.ufrgs.br:10183/205773Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2020-02-14T07:15:46Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths |
title |
Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths |
spellingShingle |
Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths Spíndola, Letícia Maria Nery Transtornos mentais Epigenômica Expressão gênica Metilação Transcrição genética Mental disorders Epigenetics Methylation Gene expression Transcription |
title_short |
Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths |
title_full |
Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths |
title_fullStr |
Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths |
title_full_unstemmed |
Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths |
title_sort |
Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths |
author |
Spíndola, Letícia Maria Nery |
author_facet |
Spíndola, Letícia Maria Nery Belangero, Síntia Iole Nogueira Rohde, Luis Augusto Paim Salum Junior, Giovanni Abrahão |
author_role |
author |
author2 |
Belangero, Síntia Iole Nogueira Rohde, Luis Augusto Paim Salum Junior, Giovanni Abrahão |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Spíndola, Letícia Maria Nery Belangero, Síntia Iole Nogueira Rohde, Luis Augusto Paim Salum Junior, Giovanni Abrahão |
dc.subject.por.fl_str_mv |
Transtornos mentais Epigenômica Expressão gênica Metilação Transcrição genética |
topic |
Transtornos mentais Epigenômica Expressão gênica Metilação Transcrição genética Mental disorders Epigenetics Methylation Gene expression Transcription |
dc.subject.eng.fl_str_mv |
Mental disorders Epigenetics Methylation Gene expression Transcription |
description |
Background: Psychiatric symptomatology during late childhood and early adolescence tends to persist later in life. In the present longitudinal study, we aimed to identify changes in genome-wide DNA methylation patterns that were associated with the emergence of psychopathology in youths from the Brazilian High-Risk Cohort (HRC) for psychiatric disorders. Moreover, for the differentially methylated genes, we verified whether differences in DNA methylation corresponded to differences in mRNA transcript levels by analyzing the gene expression levels in the blood and by correlating the variation of DNA methylation values with the variation of mRNA levels of the same individuals. Finally, we examined whether the variations in DNA methylation and mRNA levels were correlated with psychopathology measurements over time. Methods: We selected 24 youths from the HRC who presented with an increase in dimensional psychopathology at a 3-year follow-up as measured by the Child Behavior Checklist (CBCL). The DNA methylation and gene expression data were compared in peripheral blood samples (n = 48) obtained from the 24 youths before and after developing psychopathology. We implemented a methodological framework to reduce the effect of chronological age on DNA methylation using an independent population of 140 youths and the effect of puberty using data from the literature. Results: We identified 663 differentially methylated positions (DMPs) and 90 differentially methylated regions (DMRs) associated with the emergence of psychopathology. We observed that 15 DMPs were mapped to genes that were differentially expressed in the blood; among these, we found a correlation between the DNA methylation and mRNA levels of RB1CC1 and a correlation between the CBCL and mRNA levels of KMT2E. Of the DMRs, three genes were differentially expressed: ASCL2, which is involved in neurogenesis; HLA-E, which is mapped to the MHC loci; and RPS6KB1, the gene expression of which was correlated with an increase in the CBCL between the time points. Conclusions: We observed that changes in DNA methylation and, consequently, in gene expression in the peripheral blood occurred concurrently with the emergence of dimensional psychopathology in youths. Therefore, epigenomic modulations might be involved in the regulation of an individual’s development of psychopathology. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019 |
dc.date.accessioned.fl_str_mv |
2020-02-13T04:21:31Z |
dc.type.driver.fl_str_mv |
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info:eu-repo/semantics/publishedVersion |
format |
article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/205773 |
dc.identifier.issn.pt_BR.fl_str_mv |
1868-7083 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001110953 |
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http://hdl.handle.net/10183/205773 |
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eng |
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dc.relation.ispartof.pt_BR.fl_str_mv |
Clinical epigenetics. London. vol. 11 (2019), 146, 16 f. |
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openAccess |
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