Evaluating the association between placenta DNA methylation and cognitive functions in the offspring
Year: 2024
Type: article
Study design: Observational Study
Abstract: Placenta plays a crucial role protecting the foetus 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 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 were involved in placenta, foetal, and brain development. Moreover, functional enrichment analyses of suggestive CpGs (p < 1x10− 4) revealed gene-sets involved in placenta development, foetus formation and brain growth. These findings suggest that placental DNAm 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. .
Source: Translational Psychiatry
Institutions: Universitat Pompeu Fabra, Barcelona Institute for Global Health, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, University of the Basque Country, BioCruces Health research Institute, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Erasmus MC, Institut de Recerca Biomèdica Catalunya Sud, Universitat Jaume I, Universitat de València, Center for Research in Environmental Epidemiology, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Bradford Royal Infirmary, Biogipuzkoa Health Research Institute, Bradford Institute for Health Research, Basque Government
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,990
Funders: U.S. Department of Veterans Affairs, Fundación Alicia Koplowitz, Fundació la Marató de TV3, Centres de Recerca de Catalunya, European Commission, Deutsche Forschungsgemeinschaft, Generalitat de Catalunya, Eusko Jaurlaritza, Generalitat Valenciana, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, Agencia Estatal de Investigación, Ministerio de Universidades
Awards: G1012569570, G102969848, G1075404386, G1175115578, G1184738406, G1222977051, G1288326559, G1338257350, G1345005809, G1348827192, G1367041412, G1422035950, G1498169662, G1575554462, G1577542556, G1585958176, La metilación del ADN como mediador de la exposición prenatal a contaminantes obesógenos en la obesidad infantil, G1638066651, G1752229630, G1862950506, G1892331650, G1909806778, G1929206383, G2030817791, Consecuencias bioquímicas, metabólicas y genéticas de la exposición humana a disruptores endocrinos obesógenos en sujetos con obesidad y normopeso, G2064873908, G210041235, G2197905980, G2206155153, G2248009107, G2262748287, G2371386158, G2382355258, G2387096677, G2531337759, G2585906617, G2601397997, G2620658983, G2621283389, G2677176130, G2712492024, G2748727953, G281633777, G2867885658, G2880172760, G288263039, G3005324705, G300979063, G3053013269, G3061056673, G3158803353, G3221109369, G3251898604, G3297116590, Caracterización de la exposición a campos electromagnéticos de radiación no ionizante en los niños de la cohorte INMA-Gipuzkoa., G3405515844, G3423777635, G34346518, G3462794073, G3480869486, G3559709381, G3589766707, G3662005835, G3681454997, Relación entre la exposición a disruptores endocrinos, microbiota y neurodesarrollo hasta la adolescencia – Proyecto INMA-Ado-Microbiota, Efectos de la situación socioeconómica y contexto familiar en el desarrollo neuropsicológico en niños de 10-11 años de la Cohorte INMA-Valencia, G4042783231, G4106119142, G4112181810, G4141329914, G4153202515, G4206880562, G425668148, G4275577094, G4314485874, G434337789, G4353445841, Exposición a disruptores endocrinos y pubertad, G4442566642, G452346505, G4640317162, G4757997566, G4823363329, G4849428099, G4893758441, G4909233925, Advancing Tools for Human Early Lifecourse Exposome Research and Translation, G5000828053, G5025573518, G5080475149, G5185833053, G5202549584, G5208870812, G5324658026, Exposición prenatal a arsénico inorgánico y efectos en el desarrollo fetal y neuropsicológico en niños/as participantes en la cohorte INMA, G542521622, G5514740144, G5675887147, G5679630872, G5728381807, G582682078, G5852091828, G5890873539, G6033091583, G6046774704, Developmental neurotoxicity assessment of mixtures in children, G612082687, G621070573, G6328075693, G6374753769, G6412857311, G6656126374, G674505658, G6774420144, G69051668, G7053678703, G7085060884, G7208110030, G7230543579, G7288532166, G7296152096, G73640366, G740284655, G7426531139, G7427726520, G760317559, G7642116429, G7666946026, G792975244, G8035130767, G8078320960, G8167084078, G8219708615, G8227040326, G826353397, G8361113230, G845108766, G8592645448, G8597152812, G8661414666, G873757830, G8771633480, G8948884077, G903740175, G929055435
OpenAlex ID: W4402713279