Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study

Yihui Zhu, Charles E. Mordaunt, Dag H. Yasui, Ria Marathe, Rochelle L. Coulson, Keith W. Dunaway, Julia M. Jianu, Cheryl K. Walker, Sally J Ozonoff, Irva Hertz-Picciotto, Rebecca Jean Schmidt, Janine M LaSalle

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2659-2674
Number of pages16
JournalHuman molecular genetics
Volume28
Issue number16
DOIs
StatePublished - Aug 15 2019

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Cytochrome P-450 CYP2E1
DNA Methylation
Autistic Disorder
Prospective Studies
Placenta
Methylation
Genotype
High-Risk Pregnancy
Autism Spectrum Disorder
Epigenomics
Vitamins
Mothers
Learning
Parturition
Genome
Brain

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study. / Zhu, Yihui; Mordaunt, Charles E.; Yasui, Dag H.; Marathe, Ria; Coulson, Rochelle L.; Dunaway, Keith W.; Jianu, Julia M.; Walker, Cheryl K.; Ozonoff, Sally J; Hertz-Picciotto, Irva; Schmidt, Rebecca Jean; LaSalle, Janine M.

In: Human molecular genetics, Vol. 28, No. 16, 15.08.2019, p. 2659-2674.

Research output: Contribution to journalArticle

Zhu, Yihui ; Mordaunt, Charles E. ; Yasui, Dag H. ; Marathe, Ria ; Coulson, Rochelle L. ; Dunaway, Keith W. ; Jianu, Julia M. ; Walker, Cheryl K. ; Ozonoff, Sally J ; Hertz-Picciotto, Irva ; Schmidt, Rebecca Jean ; LaSalle, Janine M. / Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study. In: Human molecular genetics. 2019 ; Vol. 28, No. 16. pp. 2659-2674.
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