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Article

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

1
Departamento & Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05403-903, SP, Brazil
2
Instituto Butantan, São Paulo 05503-900, SP, Brazil
3
Laboratório de Pesquisas Básicas em Malária—Entomologia, Seção de Parasitologia—Instituto Evandro Chagas/SVS/MS, Ananindeua 66093-020, PA, Brazil
4
Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-062, SP, Brazil
5
Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie (UPM), São Paulo 01302-907, SP, Brazil
6
Departamento de Computação e Matemática FFCLRP-USP, Universidade de São Paulo, Ribeirão Preto 14040-901, SP, Brazil
7
Center for Cancer Computational Biology, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
8
Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: M. E. Suzanne Lewis
Genes 2021, 12(9), 1433; https://doi.org/10.3390/genes12091433
Received: 21 July 2021 / Revised: 3 September 2021 / Accepted: 8 September 2021 / Published: 17 September 2021
(This article belongs to the Special Issue Genetic and Phenotypic Subtypes of Autism Spectrum Disorder)
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. View Full-Text
Keywords: ASD; risk factors; vulnerability components; methylation; exome; psychiatry ASD; risk factors; vulnerability components; methylation; exome; psychiatry
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MDPI and ACS Style

Neri de Souza Reis, V.; Tahira, A.C.; Daguano Gastaldi, V.; Mari, P.; Portolese, J.; Feio dos Santos, A.C.; Lisboa, B.; Mari, J.; Caetano, S.C.; Brunoni, D.; Bordini, D.; Silvestre de Paula, C.; Vêncio, R.Z.N.; Quackenbush, J.; Brentani, H. Environmental Influences Measured by Epigenetic Clock and Vulnerability Components at Birth Impact Clinical ASD Heterogeneity. Genes 2021, 12, 1433. https://doi.org/10.3390/genes12091433

AMA Style

Neri de Souza Reis V, Tahira AC, Daguano Gastaldi V, Mari P, Portolese J, Feio dos Santos AC, Lisboa B, Mari J, Caetano SC, Brunoni D, Bordini D, Silvestre de Paula C, Vêncio RZN, Quackenbush J, Brentani H. Environmental Influences Measured by Epigenetic Clock and Vulnerability Components at Birth Impact Clinical ASD Heterogeneity. Genes. 2021; 12(9):1433. https://doi.org/10.3390/genes12091433

Chicago/Turabian Style

Neri de Souza Reis, Viviane, Ana C. Tahira, Vinícius Daguano Gastaldi, Paula Mari, Joana Portolese, Ana C. Feio dos Santos, Bianca Lisboa, Jair Mari, Sheila C. Caetano, Décio Brunoni, Daniela Bordini, Cristiane Silvestre de Paula, Ricardo Z.N. Vêncio, John Quackenbush, and Helena Brentani. 2021. "Environmental Influences Measured by Epigenetic Clock and Vulnerability Components at Birth Impact Clinical ASD Heterogeneity" Genes 12, no. 9: 1433. https://doi.org/10.3390/genes12091433

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