Language

English

Publication Date

6-22-2026

Journal

Communications Biology

DOI

10.1038/s42003-026-10500-9

PMID

42331993

PMCID

PMC13650157

PubMedCentral® Posted Date

6-22-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Early identification of autism spectrum disorder (ASD) remains a critical challenge, particularly in utero when non-genetic factors such as maternal obesity (MO) are implicated. Here, we report results of whole-genome bisulfite sequencing of cell-free DNA (cfDNA) from third-trimester maternal plasma in a high-likelihood ASD pregnancy cohort associated with child (3 y) ASD diagnosis and/or MO. Differentially methylated regions (DMRs) between ASD and control cfDNA are strongly enriched for synaptic functions and genes previously implicated in ASD. These cfDNA ASD DMRs recapitulate those observed in ASD placenta and postmortem cortex and significantly overlap with MO DMRs. Our findings establish cfDNA methylation derived from maternal blood as a minimally invasive window into fetal brain ASD etiology, providing a framework for future mechanistic and early intervention studies. Future studies could investigate additional prenatal environmental exposures interacting with genetics during neurodevelopment.

Keywords

Humans, Female, DNA Methylation, Pregnancy, Cell-Free Nucleic Acids, Pregnancy in Obesity, Autistic Disorder, Epigenome, Autism Spectrum Disorder, Adult, Predictive markers, Autism spectrum disorders

Published Open-Access

yes

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