| Full text | |
| Author(s): Show less - |
Neri de Souza Reis, Viviane
[1]
;
Tahira, Ana Carolina
[2, 1]
;
Daguano Gastaldi, Vinicius
[1]
;
Mari, Paula
[1]
;
Portolese, Joana
[1]
;
Feio dos Santos, Ana Cecilia
[1, 3]
;
Lisboa, Bianca
[1]
;
Mari, Jair
[4]
;
Caetano, Sheila C.
[4]
;
Brunoni, Decio
;
Bordini, Daniela
[4]
;
de Paula, Cristinane Silvestre
[4, 5]
;
Vencio, Ricardo Z. N.
[6]
;
Quackenbush, John
[7, 8]
;
Brentani, Helena
[1]
Total Authors: 15
|
| Affiliation: | [1] Univ Sao Paulo, Dept & Inst Psiquiatria, Fac Med FMUSP, BR-05403903 Sao Paulo, SP - Brazil
[2] Inst Butantan, BR-05503900 Sao Paulo, SP - Brazil
[3] Inst Evandro Chagas, SVS, Lab Pesquisas Basicas Malaria Entomol, Secao Parasitol, MS, BR-66093020 Ananindeua, PA - Brazil
[4] Univ Fed Sao Paulo UNIFESP, Dept Psiquiatria, BR-04023062 Sao Paulo, SP - Brazil
[5] Univ Presbiteriana Mackenzie UPM, Ctr Ciencias Biol & Saude, BR-01302907 Sao Paulo, SP - Brazil
[6] Univ Sao Paulo, Dept Computacao & Matemat, FFCLRP USP, BR-14040901 Ribeirao Preto, SP - Brazil
[7] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Ctr Canc Computat Biol, Boston, MA 02115 - USA
[8] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 - USA
Total Affiliations: 8
|
| Document type: | Journal article |
| Source: | GENES; v. 12, n. 9 SEP 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
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. (AU) | |
| FAPESP's process: | 14/00041-1 - Co-expression study among Y chromosome genes and autosomal genes and its relation to Autism Spectrum Disorders (ASD) |
| Grantee: | Ana Carolina Tahira |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 14/00591-1 - Studies of co-expression gene networks of the orbitofrontal cortex and striatum (postmortem study) of patients with OCD and controls |
| Grantee: | Bianca Cristina Garcia Lisboa |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 11/14658-2 - Copy number variation in genome of patients with obsessive-compulsive disorder and autism spectrum disorder with restricted interests and repetitive behaviors |
| Grantee: | Helena Paula Brentani |
| Support Opportunities: | Regular Research Grants |