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We sought to identify sites of DNA methylation measured at birth both responsive to periconceptional folate and associated with lymphoblasts at the time of ALL diagnosis in a \u201cmeet in the middle\u201d analysis. Folate-associated differentially methylated regions (DMRs) were identified from retrospectively collected periconceptional maternal folate intake (by dietary source) and epigenome-wide DNA methylation status from archived dried neonatal blood spots for 189 ALL cases and 205 healthy matched controls from the California Childhood Leukemia Study (1995\u20132008). Folate and lymphoblast-associated DMRs overlapped at 17 sites related to total folate intake, 13 for folate from food, 10 for natural foods, 13 for fortified foods and 18 for folate-containing supplements. The majority of overlapping DMRs were in a concordant direction of effect for supplemental folate (16\/18,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.001). Opposite direction of effect was identified among lower income participants for food (3\/19,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.004) and natural folate (5\/37,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001), the latter of which was specific to Hispanic participants of low-income (9\/31,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.029). These results indicate that dietary folate, in particular from natural food sources, may reduce risk of ALL through modulation of early DNA methylation patterns.\n                  <\/jats:p>","DOI":"10.1038\/s41375-026-02866-w","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T13:19:49Z","timestamp":1774358389000},"page":"1189-1202","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The impact of periconceptional folate on the DNA methylome of acute lymphoblastic leukemia"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5536-263X","authenticated-orcid":false,"given":"Eric M.","family":"Nickels","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1509-739X","authenticated-orcid":false,"given":"Libby M.","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8455-3481","authenticated-orcid":false,"given":"Alice Y.","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3467-4145","authenticated-orcid":false,"given":"Catherine","family":"Metayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4838-9951","authenticated-orcid":false,"given":"Joseph L.","family":"Wiemels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"2866_CR1","doi-asserted-by":"crossref","unstructured":"de Smith AJ, Spector LG. 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