Environmental Influences Measured by Epigenetic Clock and Vulnerability Components at Birth Impact Clinical ASD Heterogeneity.

Autor: Neri de Souza Reis V; Departamento & Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05403-903, SP, Brazil., Tahira AC; Departamento & Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05403-903, SP, Brazil.; Instituto Butantan, São Paulo 05503-900, SP, Brazil., Daguano Gastaldi V; Departamento & Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05403-903, SP, Brazil., Mari P; Departamento & Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05403-903, SP, Brazil., Portolese J; Departamento & Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05403-903, SP, Brazil., Feio Dos Santos AC; Departamento & Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05403-903, SP, Brazil.; Laboratório de Pesquisas Básicas em Malária-Entomologia, Seção de Parasitologia-Instituto Evandro Chagas/SVS/MS, Ananindeua 66093-020, PA, Brazil., Lisboa B; Departamento & Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05403-903, SP, Brazil., Mari J; Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-062, SP, Brazil., Caetano SC; Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-062, SP, Brazil., Brunoni D; Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie (UPM), São Paulo 01302-907, SP, Brazil., Bordini D; Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-062, SP, Brazil., Silvestre de Paula C; Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-062, SP, Brazil.; Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie (UPM), São Paulo 01302-907, SP, Brazil., Vêncio RZN; Departamento de Computação e Matemática FFCLRP-USP, Universidade de São Paulo, Ribeirão Preto 14040-901, SP, Brazil., Quackenbush J; Center for Cancer Computational Biology, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA., Brentani H; Departamento & Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05403-903, SP, Brazil.
Jazyk: angličtina
Zdroj: Genes [Genes (Basel)] 2021 Sep 17; Vol. 12 (9). Date of Electronic Publication: 2021 Sep 17.
DOI: 10.3390/genes12091433
Abstrakt: 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, adjR 2 = 0.31), suggesting risk factors with stress burden can influence ASD phenotype.
Databáze: MEDLINE
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