Environmental influences measured by epigenetic clock and vulnerability components at birth impact clinical ASD heterogeneity
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Digital do Instituto Evandro Chagas (Patuá) |
Texto Completo: | https://patua.iec.gov.br/handle/iec/4453 |
Resumo: | Although Autism Spectrum Disorders (ASD) is recognized as being heavily influenced by genetic factors, the role of epigenetic and environmental factors is still being established. This study aimed to identify ASD vulnerability components based on familial history and intrauterine environmental stress exposure, explore possible vulnerability subgroups, access DNA methylation age acceleration (AA) as a proxy of stress exposure during life, and evaluate the association of ASD vulnerability components and AA to phenotypic severity measures. Principal Component Analysis (PCA) was used to search the vulnerability components from 67 mothers of autistic children. We found that PC1 had a higher correlation with psychosocial stress (maternal stress, maternal education, and social class), and PC2 had a higher correlation with biological factors (psychiatric family history and gestational complications). Comparing the methylome between above and below PC1 average subgroups we found 11,879 statistically significant differentially methylated probes (DMPs, p < 0.05). DMPs CpG sites were enriched in variably methylated regions (VMRs), most showing environmental and genetic influences. Hypermethylated probes presented higher rates in different regulatory regions associated with functional SNPs, indicating that the subgroups may have different affected regulatory regions and their liability to disease explained by common variations. Vulnerability components score moderated by epigenetic clock AA was associated with Vineland Total score (p = 0.0036, adjR2 = 0.31), suggesting risk factors with stress burden can influence ASD phenotype |
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Reis, Viviane Neri de SouzaTahira, Ana CarolinaGastaldi, Vinícius DaguanoMari, PaulaPortolese, JoanaSantos, Ana Cecilia Feio dosLisboa, BiancaMari, JairCaetano, Sheila CBrunoni, DécioBordini, DanielaPaula, Cristiane Silvestre deVêncio, Ricardo Z. NQuackenbush, JohnBrentani, Helena2021-10-04T20:09:22Z2021-10-04T20:09:22Z2021REIS, Viviane Neri de Souza et al. Environmental influences measured by epigenetic clock and vulnerability components at birth impact clinical ASD heterogeneity. Genes, v. 12, n. 9, p, 1-21, 2021.2073-4425https://patua.iec.gov.br/handle/iec/445310.3390/genes12091433Although Autism Spectrum Disorders (ASD) is recognized as being heavily influenced by genetic factors, the role of epigenetic and environmental factors is still being established. This study aimed to identify ASD vulnerability components based on familial history and intrauterine environmental stress exposure, explore possible vulnerability subgroups, access DNA methylation age acceleration (AA) as a proxy of stress exposure during life, and evaluate the association of ASD vulnerability components and AA to phenotypic severity measures. Principal Component Analysis (PCA) was used to search the vulnerability components from 67 mothers of autistic children. We found that PC1 had a higher correlation with psychosocial stress (maternal stress, maternal education, and social class), and PC2 had a higher correlation with biological factors (psychiatric family history and gestational complications). Comparing the methylome between above and below PC1 average subgroups we found 11,879 statistically significant differentially methylated probes (DMPs, p < 0.05). DMPs CpG sites were enriched in variably methylated regions (VMRs), most showing environmental and genetic influences. Hypermethylated probes presented higher rates in different regulatory regions associated with functional SNPs, indicating that the subgroups may have different affected regulatory regions and their liability to disease explained by common variations. Vulnerability components score moderated by epigenetic clock AA was associated with Vineland Total score (p = 0.0036, adjR2 = 0.31), suggesting risk factors with stress burden can influence ASD phenotypeThis research was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) grant numbers 2012/51584-0 and 2011/14658-2 and provided scholarships to ACT (14/00041-1) and BCGL (14/00591-1). CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) provided scholarships to VNSR (PROEX #1503048 and PDSE #88881.135898/2016-01) and VDG (PROEX-1669479).Universidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria. Departamento de Psiquiatria. São Paulo, SP, Brazil.Universidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria. Departamento de Psiquiatria. São Paulo, SP, Brazil / Instituto Butantan. São Paulo, SP, Brazil.Universidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria. Departamento de Psiquiatria. São Paulo, SP, Brazil.Universidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria. Departamento de Psiquiatria. São Paulo, SP, Brazil.Universidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria. Departamento de Psiquiatria. São Paulo, SP, Brazil.Universidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria. Departamento de Psiquiatria. São Paulo, SP, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Pesquisas Básicas em Malária—Entomologia. Ananindeua, PA, Brasil.Universidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria. Departamento de Psiquiatria. São Paulo, SP, BrazilUniversidade Federal de São Paulo. Departamento de Psiquiatria. São Paulo, SP, Brazil.Universidade Federal de São Paulo. Departamento de Psiquiatria. São Paulo, SP, Brazil.Universidade Presbiteriana Mackenzie. Centro de Ciências Biológicas e da Saúde. São Paulo, SP, Brazil.Universidade Federal de São Paulo. Departamento de Psiquiatria. São Paulo, SP, Brazil / Universidade Presbiteriana Mackenzie. Centro de Ciências Biológicas e da Saúde. São Paulo, SP, Brazil.Universidade de São Paulo. Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto. Departamento de Computação e Matemática. Ribeirão Preto, SP, Brazil.Dana-Farber Cancer Institute. Department of Biostatistics and Computational Biology. Center for Cancer Computational Biology. Boston, MA, USA / Harvard T. H. Chan School of Public Health. Department of Biostatistics. Boston, MA, USA.Universidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria. Departamento de Psiquiatria. 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dc.title.pt_BR.fl_str_mv |
Environmental influences measured by epigenetic clock and vulnerability components at birth impact clinical ASD heterogeneity |
title |
Environmental influences measured by epigenetic clock and vulnerability components at birth impact clinical ASD heterogeneity |
spellingShingle |
Environmental influences measured by epigenetic clock and vulnerability components at birth impact clinical ASD heterogeneity Reis, Viviane Neri de Souza Transtorno do Espectro Autista Transtornos Mentais Estresse Oxidativo / genética |
title_short |
Environmental influences measured by epigenetic clock and vulnerability components at birth impact clinical ASD heterogeneity |
title_full |
Environmental influences measured by epigenetic clock and vulnerability components at birth impact clinical ASD heterogeneity |
title_fullStr |
Environmental influences measured by epigenetic clock and vulnerability components at birth impact clinical ASD heterogeneity |
title_full_unstemmed |
Environmental influences measured by epigenetic clock and vulnerability components at birth impact clinical ASD heterogeneity |
title_sort |
Environmental influences measured by epigenetic clock and vulnerability components at birth impact clinical ASD heterogeneity |
author |
Reis, Viviane Neri de Souza |
author_facet |
Reis, Viviane Neri de Souza Tahira, Ana Carolina Gastaldi, Vinícius Daguano Mari, Paula Portolese, Joana Santos, Ana Cecilia Feio dos Lisboa, Bianca Mari, Jair Caetano, Sheila C Brunoni, Décio Bordini, Daniela Paula, Cristiane Silvestre de Vêncio, Ricardo Z. N Quackenbush, John Brentani, Helena |
author_role |
author |
author2 |
Tahira, Ana Carolina Gastaldi, Vinícius Daguano Mari, Paula Portolese, Joana Santos, Ana Cecilia Feio dos Lisboa, Bianca Mari, Jair Caetano, Sheila C Brunoni, Décio Bordini, Daniela Paula, Cristiane Silvestre de Vêncio, Ricardo Z. N Quackenbush, John Brentani, Helena |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Reis, Viviane Neri de Souza Tahira, Ana Carolina Gastaldi, Vinícius Daguano Mari, Paula Portolese, Joana Santos, Ana Cecilia Feio dos Lisboa, Bianca Mari, Jair Caetano, Sheila C Brunoni, Décio Bordini, Daniela Paula, Cristiane Silvestre de Vêncio, Ricardo Z. N Quackenbush, John Brentani, Helena |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Transtorno do Espectro Autista Transtornos Mentais Estresse Oxidativo / genética |
topic |
Transtorno do Espectro Autista Transtornos Mentais Estresse Oxidativo / genética |
description |
Although Autism Spectrum Disorders (ASD) is recognized as being heavily influenced by genetic factors, the role of epigenetic and environmental factors is still being established. This study aimed to identify ASD vulnerability components based on familial history and intrauterine environmental stress exposure, explore possible vulnerability subgroups, access DNA methylation age acceleration (AA) as a proxy of stress exposure during life, and evaluate the association of ASD vulnerability components and AA to phenotypic severity measures. Principal Component Analysis (PCA) was used to search the vulnerability components from 67 mothers of autistic children. We found that PC1 had a higher correlation with psychosocial stress (maternal stress, maternal education, and social class), and PC2 had a higher correlation with biological factors (psychiatric family history and gestational complications). Comparing the methylome between above and below PC1 average subgroups we found 11,879 statistically significant differentially methylated probes (DMPs, p < 0.05). DMPs CpG sites were enriched in variably methylated regions (VMRs), most showing environmental and genetic influences. Hypermethylated probes presented higher rates in different regulatory regions associated with functional SNPs, indicating that the subgroups may have different affected regulatory regions and their liability to disease explained by common variations. Vulnerability components score moderated by epigenetic clock AA was associated with Vineland Total score (p = 0.0036, adjR2 = 0.31), suggesting risk factors with stress burden can influence ASD phenotype |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-10-04T20:09:22Z |
dc.date.available.fl_str_mv |
2021-10-04T20:09:22Z |
dc.date.issued.fl_str_mv |
2021 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
REIS, Viviane Neri de Souza et al. Environmental influences measured by epigenetic clock and vulnerability components at birth impact clinical ASD heterogeneity. Genes, v. 12, n. 9, p, 1-21, 2021. |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/4453 |
dc.identifier.issn.-.fl_str_mv |
2073-4425 |
dc.identifier.doi.-.fl_str_mv |
10.3390/genes12091433 |
identifier_str_mv |
REIS, Viviane Neri de Souza et al. Environmental influences measured by epigenetic clock and vulnerability components at birth impact clinical ASD heterogeneity. Genes, v. 12, n. 9, p, 1-21, 2021. 2073-4425 10.3390/genes12091433 |
url |
https://patua.iec.gov.br/handle/iec/4453 |
dc.language.iso.fl_str_mv |
eng |
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eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
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IEC |
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IEC |
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Repositório Digital do Instituto Evandro Chagas (Patuá) |
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