The early-life exposome modulates the effect of polymorphic inversions on DNA methylation

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• dc.contributor.author Carreras-Gallo, Natàlia
• dc.contributor.author Cáceres, Alejandro
• dc.contributor.author Balagué-Dobón, Laura
• dc.contributor.author Ruiz-Arenas, Carlos
• dc.contributor.author Casas Sanahuja, Maribel
• dc.contributor.author Maitre, Léa
• dc.contributor.author Nieuwenhuijsen, Mark J.
• dc.contributor.author Stratakis, Nikos
• dc.contributor.author Urquiza, José M.
• dc.contributor.author Bustamante Pineda, Mariona
• dc.contributor.author Vrijheid, Martine
• dc.contributor.author Pérez Jurado, Luis Alberto
• dc.contributor.author Gonzalez, Juan Ramon
• dc.date.accessioned 2022-06-17T10:31:53Z
• dc.date.available 2022-06-17T10:31:53Z
• dc.date.issued 2022
• dc.description.abstract Polymorphic genomic inversions are chromosomal variants with intrinsic variability that play important roles in evolution, environmental adaptation, and complex traits. We investigated the DNA methylation patterns of three common human inversions, at 8p23.1, 16p11.2, and 17q21.31 in 1,009 blood samples from children from the Human Early Life Exposome (HELIX) project and in 39 prenatal heart tissue samples. We found inversion-state specific methylation patterns within and nearby flanking each inversion region in both datasets. Additionally, numerous inversion-exposure interactions on methylation levels were identified from early-life exposome data comprising 64 exposures. For instance, children homozygous at inv-8p23.1 and higher meat intake were more susceptible to TDH hypermethylation (P = 3.8 × 10-22); being the inversion, exposure, and gene known risk factors for adult obesity. Inv-8p23.1 associated hypermethylation of GATA4 was also detected across numerous exposures. Our data suggests that the pleiotropic influence of inversions during development and lifetime could be substantially mediated by allele-specific methylation patterns which can be modulated by the exposome.
• dc.description.sponsorship The study has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no 308333 (HELIX project), and the H2020-EU.3.1.2.—Preventing Disease Programme under grant agreement no 874583 (ATHLETE project). The HELIX genotyping was supported by the projects PI17/01225 and PI17/01935, funded by the Instituto de Salud Carlos III and cofunded by 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 Economic and Social Science Research Council (ESRC) (MR/N024397/1). INMA-SAB 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 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). This research has received funding from the Spanish Ministry of Education, Innovation and Universities, the National Agency for Research and the Fund for Regional Development (RTI2018-100789-B-I00), MaratóTV3 (2015–3230), the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023 (CEX2018-000806-S) and Maria de Maeztu (MDM-2014-0370)” Programs, and support from the Generalitat de Catalunya through the CERCA and Consolidated Research Group (2017SGR01974) Programs. NC and JU are supported by Spanish regional program PERIS (Ref.: SLT017/20/000061 and SLT017/20/000119, respectively), granted by Departament de Salut de la Generalitat de Catalunya
• dc.format.mimetype application/pdf
• dc.identifier.citation Carreras-Gallo N, Cáceres A, Balagué-Dobón L, Ruiz-Arenas C, Andrusaityte S, Carracedo Á et al. The early-life exposome modulates the effect of polymorphic inversions on DNA methylation. Commun Biol. 2022 May 12;5(1):455. DOI:10.1038/s42003-022-03380-2
• dc.identifier.doi http://dx.doi.org/10.1038/s42003-022-03380-2
• dc.identifier.issn 2399-3642
• dc.identifier.uri http://hdl.handle.net/10230/53521
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/211250
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/226285
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/226756
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/241604
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP6/16320
• dc.rights © Natàlia Carreras-Gallo et al 2022. 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 license, and indicate if changes were made
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Genòmica
• dc.subject.other ADN -- Metilació
• dc.subject.other Infants
• dc.title The early-life exposome modulates the effect of polymorphic inversions on DNA methylation
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion