The multi-omics signatures of telomere length in childhood

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  • dc.contributor.author Wang, Congrong
  • dc.contributor.author Bustamante Pineda, Mariona
  • dc.contributor.author Maitre, Léa
  • dc.contributor.author Borràs, Eva
  • dc.contributor.author Sabidó Aguadé, Eduard, 1981-
  • dc.contributor.author Anguita Ruiz, Augusto
  • dc.contributor.author Pelegrí-Sisó, Dolors
  • dc.contributor.author González, Juan Ramón
  • dc.contributor.author Vrijheid, Martine
  • dc.contributor.author Nawrot, Tim S.
  • dc.date.accessioned 2025-03-24T07:15:42Z
  • dc.date.available 2025-03-24T07:15:42Z
  • dc.date.issued 2025
  • dc.description.abstract Background: Telomere length is an important indicator of biological age and a complex multi-factor trait. To date, the telomere interactome for comprehending the high-dimensional biological aspects linked to telomere regulation during childhood remains unexplored. Here we describe the multi-omics signatures associated with childhood telomere length. Methods: This study included 1001 children aged 6 to 11 years from the Human Early-life Exposome (HELIX) project. Telomere length was quantified via qPCR in peripheral blood of the children. Blood DNA methylation, gene expression, miRNA expression, plasma proteins and serum and urinary metabolites were measured through microarrays or (semi-) targeted assays. The association between each individual omics feature and telomere length was assessed in omics-wide association analyses. In addition, a literature-guided, sparse supervised integration method was applied to multiple omics, and latent components were extracted as predictors of child telomere length. The association of these latent components with early-life aging risk factors (child lifestyle, body mass index (BMI), exposure to smoking, etc.), were interrogated. Results: After multiple-testing correction, only two CpGs (cg23686403 and cg16238918 at PARD6G gene) out of all the omics features were significantly associated with child telomere length. The supervised multi-omics integration approach revealed robust associations between latent components and child BMI, with metabolites and proteins emerging as the primary contributing features. In these latent components, the contributing molecular features were known as involved in metabolism and immune regulation-related pathways. Conclusions: Findings of this multi-omics study suggested an intricate interplay between telomere length, metabolism and immune responses, providing valuable insights into the molecular underpinnings of the early-life biological aging.
  • dc.description.sponsorship The study has 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). The genotyping was supported by the projects PI17/01225 and PI17/01935, funded by the Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union (ERDF, “A way to make Europe”) and the Centro Nacional de Genotipado-CEGEN (PRB2-ISCIII). BiB received core infrastructure funding from the Wellcome Trust (WT101597MA) and a joint grant from the UK Medical Research Council (MRC) and the Economic and Social Science Research Council (ESRC) (MR/N024397/1). 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 a grant from the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). 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. 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 Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. L.M. is funded by a Juan de la Cierva-Incorporación fellowship (IJC2018-035394-I) awarded by the Spanish Ministerio de Economía, Industria y Competitividad. The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech). D.S.M. holds a postdoctoral grant from the Research Foundations Flanders (FWO grants 12 × 9623 N).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Wang C, Martens DS, Bustamante M, Alfano R, Plusquin M, Maitre L, et al. The multi-omics signatures of telomere length in childhood. BMC Genomics. 2025 Jan 27;26(1):75. DOI: 10.1186/s12864-025-11209-5
  • dc.identifier.doi http://dx.doi.org/10.1186/s12864-025-11209-5
  • dc.identifier.issn 1471-2164
  • dc.identifier.uri http://hdl.handle.net/10230/69994
  • dc.language.iso eng
  • dc.publisher BioMed Central
  • dc.relation.ispartof BMC Genomics. 2025 Jan 27;26(1):75
  • 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/2PE/CEX2018-000806-S
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/IJC2018-035394-I
  • 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 Biological aging
  • dc.subject.keyword Early-life
  • dc.subject.keyword Multi-omics
  • dc.subject.keyword Telomere length
  • dc.title The multi-omics signatures of telomere length in childhood
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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