Prenatal cell-free DNA methylome detects association with autism and maternal obesity

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 were strongly enriched for synaptic functions and genes previously implicated in ASD.

These cfDNA ASD DMRs recapitulated those observed in ASD placenta and postmortem cortex and significantly overlapped 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.