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We aimed to examine whether placental asparaginase (\n                      <jats:italic>ASPG<\/jats:italic>\n                      ) DNA methylation (DNAm) is associated with adiposity at 6\u00a0years of age and to explore its cross-tissue patterns and parent\u2013child concordance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a prospective birth cohort, placental\n                      <jats:italic>ASPG<\/jats:italic>\n                      DNAm was quantified by pyrosequencing and related to anthropometric and cardiometabolic outcomes in children at 6\u00a0years (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009180). DNAm was also measured in child peripheral blood (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009127) and in maternal and paternal blood samples during pregnancy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200944).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Increased placental\n                      <jats:italic>ASPG<\/jats:italic>\n                      DNAm was associated with increased adiposity and cardiometabolic markers at 6\u00a0years and increased odds of overweight\/obesity [odds ratio (OR)\u2009=\u20091.06, 95% confidence interval (CI)\u2009=\u20091.01\u20131.11,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.01]. Similar associations were observed for child blood (OR\u2009=\u20091.19, 95% CI\u2009=\u20091.04\u20131.36,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.01), although these analyses were cross-sectional. Placental and child DNAm levels were positively correlated (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.40,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.01), and maternal\u2013child DNAm was concordant (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.48,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.01), although the parental analyses were exploratory and based on a limited sample size (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200944).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ASPG<\/jats:italic>\n                      DNAm is associated with childhood adiposity and shows cross-tissue and parent\u2013child concordance, suggesting its potential role as an early-life epigenetic marker associated with metabolic risk. Given the modest effect sizes and exploratory nature of some analyses, these findings warrant cautious interpretation and require replication in independent cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12519-026-01071-0","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:24:52Z","timestamp":1789471492000},"page":"899-909","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Asparaginase methylation and childhood obesity: cross-tissue patterns and parent\u2013child concordance in a prospective cohort"],"prefix":"10.1007","volume":"22","author":[{"given":"Maria","family":"Niub\u00f3-Pall\u00e0s","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariadna","family":"G\u00f3mez-Vilarrubla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falia","family":"Moll\u00e0-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Mas-Pares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Bonmat\u00ed-Santan\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9-Mar\u00eda","family":"Mart\u00ednez-Calcerrada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"de Zegher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5828-8911","authenticated-orcid":false,"given":"Abel","family":"L\u00f3pez-Bermejo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8821-6655","authenticated-orcid":false,"given":"Judit","family":"Bassols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"1071_CR1","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/s12916-019-1449-8","volume":"17","author":"M Di Cesare","year":"2019","unstructured":"Di Cesare M, Sori\u0107 M, Bovet P, Miranda JJ, Bhutta Z, Stevens GA, et al. 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