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In utero and childhood exposure to tobacco smoke and multi-layer molecular signatures in children

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dc.contributor.author Vives Usano, Marta, 1990-
dc.contributor.author Hernández-Ferrer, Carles
dc.contributor.author Maitre, Léa
dc.contributor.author Ruiz Arenas, Carlos, 1990-
dc.contributor.author Borràs, Eva
dc.contributor.author Casas Sanahuja, Maribel
dc.contributor.author Estivill, Xavier, 1955-
dc.contributor.author González, Juan Ramón
dc.contributor.author Sabidó Aguadé, Eduard, 1981-
dc.contributor.author Vrijheid, Martine
dc.contributor.author Bustamante Pineda, Mariona
dc.date.accessioned 2020-10-27T06:49:37Z
dc.date.available 2020-10-27T06:49:37Z
dc.date.issued 2020
dc.identifier.citation Vives-Usano M, Hernandez-Ferrer C, Maitre L, Ruiz-Arenas C, Andrusaityte S, Borràs E et al. In utero and childhood exposure to tobacco smoke and multi-layer molecular signatures in children. BMC Med. 2020; 18(1):243. DOI: 10.1186/s12916-020-01686-8
dc.identifier.issn 1741-7015
dc.identifier.uri http://hdl.handle.net/10230/45579
dc.description.abstract Background: The adverse health effects of early life exposure to tobacco smoking have been widely reported. In spite of this, the underlying molecular mechanisms of in utero and postnatal exposure to tobacco smoke are only partially understood. Here, we aimed to identify multi-layer molecular signatures associated with exposure to tobacco smoke in these two exposure windows. Methods: We investigated the associations of maternal smoking during pregnancy and childhood secondhand smoke (SHS) exposure with molecular features measured in 1203 European children (mean age 8.1 years) from the Human Early Life Exposome (HELIX) project. Molecular features, covering 4 layers, included blood DNA methylation and gene and miRNA transcription, plasma proteins, and sera and urinary metabolites. Results: Maternal smoking during pregnancy was associated with DNA methylation changes at 18 loci in child blood. DNA methylation at 5 of these loci was related to expression of the nearby genes. However, the expression of these genes themselves was only weakly associated with maternal smoking. Conversely, childhood SHS was not associated with blood DNA methylation or transcription patterns, but with reduced levels of several serum metabolites and with increased plasma PAI1 (plasminogen activator inhibitor-1), a protein that inhibits fibrinolysis. Some of the in utero and childhood smoking-related molecular marks showed dose-response trends, with stronger effects with higher dose or longer duration of the exposure. Conclusion: In this first study covering multi-layer molecular features, pregnancy and childhood exposure to tobacco smoke were associated with distinct molecular phenotypes in children. The persistent and dose-dependent changes in the methylome make CpGs good candidates to develop biomarkers of past exposure. Moreover, compared to methylation, the weak association of maternal smoking in pregnancy with gene expression suggests different reversal rates and a methylation-based memory to past exposures. Finally, certain metabolites and protein markers evidenced potential early biological effects of postnatal SHS, such as fibrinolysis.
dc.description.sponsorship The study has received funding from the European Community’s Seventh Framework Programme (FP7/2007-206) under grant agreement no. 308333 (the HELIX project); and the H2020-EU.3.1.2. - Preventing Disease Programme under grant agreement no 874583 (the ATHLETE project). 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). 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 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 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: 2012–2015). The work was also supported by MICINN (MTM2015-68140-R) and Centro Nacional de Genotipado-CEGEN-PRB2-ISCIII. The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech), and it is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I+D+i 2013-2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF. We acknowledge 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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartof BMC Med. 2020; 18(1):243
dc.rights © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. 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/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data ma
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title In utero and childhood exposure to tobacco smoke and multi-layer molecular signatures in children
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/s12916-020-01686-8
dc.subject.keyword Children
dc.subject.keyword DNA methylation
dc.subject.keyword Metabolomics
dc.subject.keyword Molecular phenotypes
dc.subject.keyword Omics
dc.subject.keyword Pregnancy
dc.subject.keyword Secondhand smoke
dc.subject.keyword Tobacco smoking
dc.subject.keyword Transcription
dc.subject.keyword miRNA
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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