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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths

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Spindola, Leticia M. [1, 2, 3] ; Santoro, Marcos L. [1, 2, 3] ; Pan, Pedro M. [1, 3] ; Ota, Vanessa K. [2, 3] ; Xavier, Gabriela [2, 3] ; Carvalho, Carolina M. [1, 2, 3] ; Talarico, Fernanda [2, 3] ; Sleiman, Patrick [4] ; March, Michael [4] ; Pellegrino, Renata [4] ; Brietzke, Elisa [1] ; Grassi-Oliveira, Rodrigo [5] ; Mari, Jair J. [1, 3] ; Gadelha, Ary [1, 3] ; Miguel, Euripedes C. [6] ; Rohde, Luis A. [7] ; Bressan, Rodrigo A. [1, 3] ; Mazzotti, Diego R. [8] ; Sato, Joao R. [9] ; Salum, Giovanni A. [7] ; Hakonarson, Hakon [4] ; Belangero, I, Sintia
Total Authors: 22
Affiliation:
[1] I, Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo - Brazil
[2] I, Univ Fed Sao Paulo UNIFESP, Dept Morphol & Genet, Genet Div, Rua Botucatu 740, Sao Paulo, SP - Brazil
[3] I, Univ Fed Sao Paulo, LiNC Lab Integrat Neurosci, Sao Paulo - Brazil
[4] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 - USA
[5] Pontificia Univ Catolica Rio Grande do Sul PUCRS, Brain Inst, Porto Alegre, RS - Brazil
[6] Univ Sao Paulo, Fac Med, Dept Psychiat, Sao Paulo - Brazil
[7] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Dept Psychiat, Porto Alegre, RS - Brazil
[8] Univ Penn, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 - USA
[9] Univ Fed ABC, Ctr Math Comp & Cognit, Santo Andre - Brazil
Total Affiliations: 9
Document type: Journal article
Source: CLINICAL EPIGENETICS; v. 11, n. 1 OCT 21 2019.
Web of Science Citations: 0
Abstract

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. (AU)

FAPESP's process: 16/04983-7 - Neuroimaging, genomics, transcriptomics and epigenomics: dealing with big data toward an integrative model of mental disorders
Grantee:Jair de Jesus Mari
Support type: Research Grants - eScience and Data Science Program - Regular Program Grants
FAPESP's process: 14/50917-0 - INCT 2014: developmental psychiatry for children and adolescents
Grantee:Eurípedes Constantino Miguel Filho
Support type: Research Projects - Thematic Grants
FAPESP's process: 15/10733-0 - Analysis of DNA methylation in blood associated with emergence of psychiatric symptoms and environmental stressors in adolescence
Grantee:Leticia Maria Nery Spindola
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 16/25374-9 - Methylomic changes during development of psychiatric disorders
Grantee:Leticia Maria Nery Spindola
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 17/05339-7 - Characterization of gene expression profiles in children and adolescents at risk for mental disorders
Grantee:Vanessa Kiyomi Ota Kuniyoshi
Support type: Regular Research Grants
FAPESP's process: 14/07280-1 - Search for genetic markers of risk, progression and response to treatment
Grantee:Síntia Iole Nogueira Belangero
Support type: Regular Research Grants