Meet-in-the-middle meets multi-omics identifying molecular signatures of environmental drivers of childhood overweight
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- dc.contributor.author Wang, Congrong
- dc.contributor.author Sunyer Deu, Jordi
- dc.contributor.author Borràs, Eva
- dc.contributor.author Sabidó Aguadé, Eduard, 1981-
- dc.contributor.author González, Juan Ramón
- dc.contributor.author Vives Usano, Marta, 1990-
- dc.contributor.author Estivill, Xavier, 1955-
- dc.contributor.author Casas Sanahuja, Maribel
- dc.contributor.author Nieuwenhuijsen, Mark J.
- dc.contributor.author Bustamante Pineda, Mariona
- dc.contributor.author Maitre, Léa
- dc.contributor.author Vrijheid, Martine
- dc.contributor.author Alfano, Rossella
- dc.date.accessioned 2025-09-18T06:17:59Z
- dc.date.available 2025-09-18T06:17:59Z
- dc.date.issued 2025
- dc.description.abstract Background: Obesity is a multi-cause chronic disease recognized across the lifespan, with childhood obesity prevalence rising over the past decades. Although exposome-wide association studies have identified early-life environmental drivers of child obesity, and explored the multi-omics signatures of the exposome of children, it is understudied whether the combined effects of multiple exposures are potentially mediated by multi-omics. Methods: Within the Human Early Life Exposome (HELIX) project, 1041 mother-child pairs were surveyed for a wide range of environmental exposures including over 354 prenatal and childhood exposures. Multi-omics molecular features were measured during childhood, encompassing the blood methylome and transcriptome, plasma proteins and urinary and serum metabolites. Exposome and multi-omics features were integrated into latent factors by Multi-omics Factor Analysis, based on which structural equation modelling was used to assess whether multi-omics mediated associations between exposome and child body mass index (BMI). Results: Key findings included: (i) prenatal nutrition, exercise, and passive smoking influencing BMI via DNA methylation of HOXA5 and Tenascin XB; (ii) childhood exposure to PCBs and phenols linked with BMI through inflammation and coagulation pathways; and (iii) childhood PCB and dietary exposures associated with BMI via immune pathways. Conclusions: This novel untargeted workflow elucidated biological mechanisms linking environmental exposures to child obesity, potentially supporting targeted public health interventions.
- dc.description.sponsorship The study has received funding from the European Union’s Horizon 2020 research and innovation programme, European Union, under grant agreement No 874583 (ATHLETE project). Data were collected as part of the European Community’s Seventh Framework Programme (FP7/2007-206), European Union, under grant agreement no 308333 (HELIX project). BiB is supported by a joint grant from the UK Medical Research Council (MRC) and UK Economic and Social Science Research Council (ESRC) (MR/N024391/1), United Kingdom; the British Heart Foundation (CS/16/4/32482), United Kingdom; a Wellcome Infrastructure Grant (WT101597MA), United Kingdom; the National Institute for Health Research under its Applied Research Collaboration for Yorkshire and Humber (NIHR200166), United Kingdom. The National Institute for Health Research Clinical Research Network, United Kingdom, provided research delivery support for this study. INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT, Spain. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66), Lithuania. The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, Norway. 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, European Union), and the Greek Ministry of Health, Greece (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). The CRG/UPF Proteomics Unit is part of the Spanish National Infrastructure for Omics Sciences (ICTS OmicsTech), Spain.
- dc.format.mimetype application/pdf
- dc.identifier.citation Wang C, Reimann B, Nawrot TS, Martens DS, Wright J, McEachan R, et al. Meet-in-the-middle meets multi-omics identifying molecular signatures of environmental drivers of childhood overweight. Environ Int. 2025 Aug;202:109630. DOI: 10.1016/j.envint.2025.109630
- dc.identifier.doi http://dx.doi.org/10.1016/j.envint.2025.109630
- dc.identifier.issn 0160-4120
- dc.identifier.uri http://hdl.handle.net/10230/71219
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Environ Int. 2025 Aug;202:109630
- 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.rights © 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Childhood obesity
- dc.subject.keyword Exposome
- dc.subject.keyword HELIX
- dc.subject.keyword MOFA
- dc.subject.keyword Meet-in-the-middle
- dc.subject.keyword Multi-omics
- dc.title Meet-in-the-middle meets multi-omics identifying molecular signatures of environmental drivers of childhood overweight
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion