Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study.
Autism Spectrum Disorder
/ etiology
Autistic Disorder
/ etiology
Biomarkers
Cadherins
/ metabolism
Case-Control Studies
Child
Cytochrome P-450 CYP2E1
/ genetics
DNA Methylation
Disease Susceptibility
Epigenesis, Genetic
Female
Gene Expression Profiling
Genome-Wide Association Study
Humans
Insulin Receptor Substrate Proteins
/ genetics
Male
Maternal Exposure
Placenta
/ metabolism
Pregnancy
Prenatal Exposure Delayed Effects
Risk
Signal Transduction
Wnt Proteins
/ metabolism
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
15 08 2019
15 08 2019
Historique:
received:
25
01
2019
revised:
25
03
2019
accepted:
15
04
2019
pubmed:
23
4
2019
medline:
10
3
2020
entrez:
23
4
2019
Statut:
ppublish
Résumé
DNA methylation acts at the interface of genetic and environmental factors relevant for autism spectrum disorder (ASD). Placenta, normally discarded at birth, is a potentially rich source of DNA methylation patterns predictive of ASD in the child. Here, we performed whole methylome analyses of placentas from a prospective study MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) of high-risk pregnancies. A total of 400 differentially methylated regions (DMRs) discriminated placentas stored from children later diagnosed with ASD compared to typically developing controls. These ASD DMRs were significantly enriched at promoters, mapped to 596 genes functionally enriched in neuronal development, and overlapped genetic ASD risk. ASD DMRs at CYP2E1 and IRS2 reached genome-wide significance, replicated by pyrosequencing and correlated with expression differences in brain. Methylation at CYP2E1 associated with both ASD diagnosis and genotype within the DMR. In contrast, methylation at IRS2 was unaffected by within DMR genotype but modified by preconceptional maternal prenatal vitamin use. This study therefore identified two potentially useful early epigenetic markers for ASD in placenta.
Identifiants
pubmed: 31009952
pii: 5476403
doi: 10.1093/hmg/ddz084
pmc: PMC6687952
doi:
Substances chimiques
Biomarkers
0
Cadherins
0
IRS2 protein, human
0
Insulin Receptor Substrate Proteins
0
Wnt Proteins
0
Cytochrome P-450 CYP2E1
EC 1.14.13.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2659-2674Subventions
Organisme : NIEHS NIH HHS
ID : R01 ES029213
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD079125
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES023513
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES025574
Pays : United States
Organisme : NIH HHS
ID : UG3 OD023365
Pays : United States
Organisme : ODCDC CDC HHS
ID : UG3 OD023365
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007377
Pays : United States
Organisme : ODCDC CDC HHS
ID : UH3 OD023365
Pays : United States
Organisme : NIEHS NIH HHS
ID : R24 ES028533
Pays : United States
Organisme : NIH HHS
ID : UH3 OD023365
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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