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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\u2009y) 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.\n                  <\/jats:p>","DOI":"10.1038\/s42003-026-10500-9","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T21:06:49Z","timestamp":1782162409000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prenatal cell-free DNA methylome detects association with autism and maternal obesity"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9797-3567","authenticated-orcid":false,"given":"Logan A.","family":"Williams","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5425-4095","authenticated-orcid":false,"given":"Ensieh","family":"Habibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irva","family":"Hertz-Picciotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl K.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1582-2747","authenticated-orcid":false,"given":"Rebecca J.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3480-2031","authenticated-orcid":false,"given":"Janine M.","family":"LaSalle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"10500_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.ss7402a1","volume":"74","author":"KA Shaw","year":"2025","unstructured":"Shaw, K. 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LaSalle is the co-founder and Chief Scientific Officer of 2C Bioscience. The Regents of the University of California have filed a U.S. provisional patent application on behalf of inventors LA Williams and JM LaSalle (#63\/972,030, pending) on the cell-free DNA methods and systems to determine neurodevelopmental risk in newborns associated with maternal obesity. All other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"1319"}}