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 J. Schmidt; Janine M. LaSalle

doi:10.1093/hmg/ddz084

GeneticsHuman Molecular GeneticsApr 17, 2019

Peer-reviewed journal article

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

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

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 of high-risk pregnancies. 400 differentially methylated regions (DMRs) discriminated placentas stored from children later diagnosed with ASD compared to typical 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. Methylation at CYP2E1 associated with both ASD diagnosis and cis genotype, while methylation at IRS2 was unaffected by cis genotype but modified by preconceptional maternal prenatal vitamin use. This study therefore identified two potentially useful early epigenetic markers for ASD in placenta.

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