Evaluating the association between placenta DNA methylation and cognitive functions in the offspring

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  • dc.contributor.author Diez-Ahijado, Laia
  • dc.contributor.author Cilleros-Portet, Ariadna
  • dc.contributor.author Fernández-Jiménez, Nora
  • dc.contributor.author Fernández, Mariana F.
  • dc.contributor.author Guxens Junyent, Mònica
  • dc.contributor.author Julvez, Jordi
  • dc.contributor.author Llop, Sabrina
  • dc.contributor.author Lopez-Espinosa, Maria-José
  • dc.contributor.author Subiza-Pérez, Mikel
  • dc.contributor.author Lozano, Manuel
  • dc.contributor.author Ibarluzea, Jesús
  • dc.contributor.author Sunyer Deu, Jordi
  • dc.contributor.author Bustamante Pineda, Mariona
  • dc.contributor.author Cosín Tomàs, Marta
  • dc.date.accessioned 2024-11-26T07:34:45Z
  • dc.date.available 2024-11-26T07:34:45Z
  • dc.date.issued 2024
  • dc.description.abstract The placenta plays a crucial role in protecting the fetus from environmental harm and supports the development of its brain. In fact, compromised placental function could predispose an individual to neurodevelopmental disorders. Placental epigenetic modifications, including DNA methylation, could be considered a proxy of placental function and thus plausible mediators of the association between intrauterine environmental exposures and genetics, and childhood and adult mental health. Although neurodevelopmental disorders such as autism spectrum disorder have been investigated in relation to placenta DNA methylation, no studies have addressed the association between placenta DNA methylation and child's cognitive functions. Thus, our goal here was to investigate whether the placental DNA methylation profile measured using the Illumina EPIC array is associated with three different cognitive domains (namely verbal score, perceptive performance score, and general cognitive score) assessed by the McCarthy Scales of Children's functions in childhood at age 4. To this end, we conducted epigenome-wide association analyses, including data from 255 mother-child pairs within the INMA project, and performed a follow-up functional analysis to help the interpretation of the findings. After multiple-testing correction, we found that methylation at 4 CpGs (cg1548200, cg02986379, cg00866476, and cg14113931) was significantly associated with the general cognitive score, and 2 distinct differentially methylated regions (DMRs) (including 27 CpGs) were significantly associated with each cognitive dimension. Interestingly, the genes annotated to these CpGs, such as DAB2, CEP76, PSMG2, or MECOM, are involved in placenta, fetal, and brain development. Moreover, functional enrichment analyses of suggestive CpGs (p < 1 × 10-4) revealed gene sets involved in placenta development, fetus formation, and brain growth. These findings suggest that placental DNA methylation could be a mechanism contributing to the alteration of important pathways in the placenta that have a consequence on the offspring's brain development and cognitive function.
  • dc.description.sponsorship We acknowledge support from the grant CEX2018-000806-S funded by MCIN/AEI/10.13039/501100011033, from the Generalitat de Catalunya through the CERCA Programme; and from the European Union’s Horizon 2020 research and innovation programme-EU.3.1.2. (874583–ATHLETE project); grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: ISCIII (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI12/00610, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663, PI16/1288 and PI1338;; Miguel Servet-FEDER CP11/00178, CP15/00025, MS20/0005, and CPII16/00051, G03/176; Generalitat Valenciana (CIAICO/2021/132): FISABIO (UGP-15-230, UGP-15-244, and UGP-15-249), Ministry of Universities (CAS21/00008 and NextGeneration EU), and Alicia Koplowitz Foundation 2017; grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430); grants from Instituto de Salud Carlos III (PI06/0867, PI11/00610, FIS-PI09/00090, FIS-PI13/02187, FIS-PI13/02406, and FIS-PI18/01142 incl. FEDER funds), CIBERESP, Department of Health of the Basque Government (2005111093, 2009111069, 2013111089 and 2015111065), Provincial Government of Gipuzkoa (DFG06/002), and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). MG was funded by a Miguel Servet-II fellowship (CPII18/00018) awarded by the Spanish Institute of Health Carlos III. MCT is funded by a Beatriu de Pinós Postdoctoral Contract awarded by Generalitat de Catalunya-AGAUR and European Commission-Horizon 2020 (2019 BP 00107). JJ was funded by a Miguel Servet-II fellowship (CPII19/00015) awarded by the Instituto de Salud Carlos III (Co-funded by the European Union Social Fund “Investing in your future”). We acknowledge all volunteers participating in the study, and interviewers and psychologists.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Diez-Ahijado L, Cilleros-Portet A, Fernández-Jimenez N, Fernández MF, Guxens M, Julvez J, et al. Evaluating the association between placenta DNA methylation and cognitive functions in the offspring. Transl Psychiatry. 2024 Sep 20;14(1):383. DOI: 10.1038/s41398-024-03094-5
  • dc.identifier.doi http://dx.doi.org/10.1038/s41398-024-03094-5
  • dc.identifier.issn 2158-3188
  • dc.identifier.uri http://hdl.handle.net/10230/68816
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Transl Psychiatry. 2024 Sep 20;14(1):383
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/282957
  • dc.rights © The Author(s) 2024. 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 Epigenetics and behaviour
  • dc.subject.keyword Personalized medicine
  • dc.title Evaluating the association between placenta DNA methylation and cognitive functions in the offspring
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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