Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants

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  • dc.contributor.author Stratakis, Nikos
  • dc.contributor.author Anguita Ruiz, Augusto
  • dc.contributor.author Fabbri, Lorenzo
  • dc.contributor.author Maitre, Léa
  • dc.contributor.author González, Juan Ramón
  • dc.contributor.author Basagaña Flores, Xavier
  • dc.contributor.author Borràs, Eva
  • dc.contributor.author Nieuwenhuijsen, Mark J.
  • dc.contributor.author Sabidó Aguadé, Eduard, 1981-
  • dc.contributor.author Urquiza, José M.
  • dc.contributor.author Bustamante Pineda, Mariona
  • dc.contributor.author Vrijheid, Martine
  • dc.date.accessioned 2025-02-25T07:32:59Z
  • dc.date.available 2025-02-25T07:32:59Z
  • dc.date.issued 2025
  • dc.description.abstract Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications. This high-risk cluster exhibits a complex interplay across many biological pathways, predominantly underscored by inflammation-related cascades. Further, by incorporating comprehensive information from the environmental risk-scape of the critical pregnancy period, we identify pre-pregnancy body mass index and environmental pollutants like perfluorooctanoate and mercury as important determinants of the high-risk cluster. Overall, our work helps to identify potential risk factors for prevention and intervention strategies early in the life course aimed at mitigating obesity and its long-term health consequences.
  • dc.description.sponsorship The study received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 874583 (ATHLETE project). Data were collected as part of the European Community’s Seventh Framework Programme (FP7/2007-206) under grant agreement no. 308333 (HELIX project). This project also received support from Generalitat de Catalunya through the Consolidated Group on HEALTH ANALYTICS (2021 SGR 01563). We would like to thank all the families whose data were used. BiB received core infrastructure funding from the Wellcome Trust (WT101597MA) and a joint grant from the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) (MR/N024397/1). The EDEN study was supported by Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A), and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programmes (FP7/2007–2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l’Education Nationale a complementary health insurance (MGEN), French national agency for food security, French-speaking association for the study of diabetes and metabolism (ALFEDIAM). INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Norwegian Mother, Father and Child Cohort Study (Moba) is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. The RHEA project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU- FP7- HEALTH-2012 Proposal No 308333 HELIX), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011-2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-15). ISGlobal acknowledges support from the grant CEX2023-0001290-S funded by MCIN/AEI/ 10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Program. Nikos Stratakis has received funding from the European Union’s Horizon Europe research and innovation programme under the Marie Skłodowska-Curie Actions (MSCA) Postdoctoral Fellowships (grant no. 101059245), by a Juan de la Cierva-Incorporación fellowship (IJC2020-043630-I) financed by Ministerio de Ciencia e Innovación (MCIN)/Agencia Estatal de Investigación (AEI)/10.13039/501100011033 and the European Union “NextGenerationEU/PRTR”, and from the Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Stratakis N, Anguita-Ruiz A, Fabbri L, Maitre L, González JR, Andrusaityte S, et al. Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants. Nat Commun. 2025 Jan 14;16(1):654. DOI: 10.1038/s41467-025-56013-7
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-025-56013-7
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/69728
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Commun. 2025 Jan 14;16(1):654
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/211250
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/226285
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/CEX2023-0001290-S
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101059245
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000806-S
  • dc.rights © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Biomarkers
  • dc.subject.keyword Obesity
  • dc.subject.keyword Risk factors
  • dc.title Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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