{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:06:20Z","timestamp":1792065980149,"version":"4.4.0"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Ministerio de Ciencia e Innovaci\u00f3n, Instituto de Salud Carlos III (ISCIII), Madrid, Spain","doi-asserted-by":"publisher","award":["PI20\/00399"],"award-info":[{"award-number":["PI20\/00399"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Ministerio de Ciencia e Innovaci\u00f3n, Instituto de Salud Carlos III (ISCIII), Madrid, Spain","doi-asserted-by":"publisher","award":["PI23\/00545"],"award-info":[{"award-number":["PI23\/00545"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FEDER","award":["PI20\/00399"],"award-info":[{"award-number":["PI20\/00399"]}]},{"name":"FEDER","award":["PI23\/00545"],"award-info":[{"award-number":["PI23\/00545"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Accumulating evidence suggests that the predisposition to metabolic diseases is established in utero through epigenomic modifications. However, it remains unclear whether childhood obesity results from preexisting epigenomic alterations or whether obesity itself induces changes in the epigenome. This study aimed to identify DNA methylation marks in the placenta associated with obesity-related outcomes in children at age 6 and to assess these marks in blood samples at age 6 and whether they correlate with obesity-related outcomes at that time. Using an epigenome-wide DNA methylation microarray on 24 placental samples, we identified differentially methylated CpGs (DMCs) associated with offspring BMI-SDS at 6 years. Individual DMCs were validated in 147 additional placental and leukocyte samples from children at 6 years of age. The methylation and\/or gene expression of IRS1 in both placenta and offspring leukocytes were significantly associated with various metabolic risk parameters at age 6 (all p \u2264 0.05). Logistic regression models (LRM) and machine learning (ML) models indicated that IRS1 methylation in the placenta could strongly predict offspring obesity. Our results suggest that IRS1 may serve as a potential biomarker for the prediction of obesity and metabolic risk in children.<\/jats:p>","DOI":"10.3390\/ijms26073141","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T13:36:49Z","timestamp":1743169009000},"page":"3141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Longitudinal Analysis of Placental IRS1 DNA Methylation and Childhood Obesity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8183-5218","authenticated-orcid":false,"given":"Ariadna","family":"G\u00f3mez-Vilarrubla","sequence":"first","affiliation":[{"name":"Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2331-0218","authenticated-orcid":false,"given":"Maria","family":"Niub\u00f3-Pall\u00e0s","sequence":"additional","affiliation":[{"name":"Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8283-3089","authenticated-orcid":false,"given":"Berta","family":"Mas-Par\u00e9s","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4354-7773","authenticated-orcid":false,"given":"Alexandra","family":"Bonmat\u00ed-Santan\u00e9","sequence":"additional","affiliation":[{"name":"Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain"},{"name":"Department of Gynecology, Dr. Josep Trueta Hospital, 17007 Girona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose-Maria","family":"Mart\u00ednez-Calcerrada","sequence":"additional","affiliation":[{"name":"Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9210-0073","authenticated-orcid":false,"given":"Beatriz","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Control Engineering and Intelligent Systems (eXiT), University of Girona, 17003 Girona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Pe\u00f1as-Cruz","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"de Zegher","sequence":"additional","affiliation":[{"name":"Department of Development and Regeneration, University of Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4595-7191","authenticated-orcid":false,"given":"Lourdes","family":"Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Endocrinology, Pediatric Research Institute, Sant Joan de D\u00e9u Children\u2019s Hospital, 08950 Esplugues de Llobregat, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel","family":"L\u00f3pez-Bermejo","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain"},{"name":"Department of Pediatrics, Dr. Josep Trueta Hospital, 17007 Girona, Spain"},{"name":"Department of Medical Sciences, University of Girona, 17003 Girona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8821-6655","authenticated-orcid":false,"given":"Judit","family":"Bassols","sequence":"additional","affiliation":[{"name":"Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e192430","DOI":"10.1001\/jamapediatrics.2019.2430","article-title":"Prevalence and Trends of Overweight and Obesity in European Children From 1999 to 2016: A Systematic Review and Meta-analysis","volume":"173","author":"Moreno","year":"2019","journal-title":"JAMA 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