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Associations between placental DNA methylation and emotional and behavioral outcomes in preschoolers: insights from the EDEN Mother-Child Cohort study

Published online by Cambridge University Press:  19 July 2023

A. Nakamura ,
L. Broseus ,
J. Tost ,
D. Vaiman ,
S. Martins ,
K. Keyes ,
K. Bonello ,
M. Fekom ,
K. Strandberg-Larsen  and
A.-L. Sutter-Dallay
...Show all authors
A. Nakamura*
Affiliation:
Institute for Advanced Biosciences (IAB), INSERM, La Tronche
L. Broseus
Affiliation:
Institute for Advanced Biosciences (IAB), INSERM, La Tronche
J. Tost
Affiliation:
Institut de Biologie François Jacob, CEA, Evry
D. Vaiman
Affiliation:
Genomics, Epigenetics and Physiopathology of Reproduction, INSERM, Paris, France
S. Martins
Affiliation:
Department of Epidemiology, Columbia University Mailman School of Public Health, New York, United States
K. Keyes
Affiliation:
Department of Epidemiology, Columbia University Mailman School of Public Health, New York, United States
K. Bonello
Affiliation:
Institut Pierre Louis d’Epidémiologie et de Santé Publique (IPLESP), INSERM School of Medicine, Department of general practice, Sorbonne Université, Paris, France
M. Fekom
Affiliation:
Institut Pierre Louis d’Epidémiologie et de Santé Publique (IPLESP), INSERM
K. Strandberg-Larsen
Affiliation:
Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
A.-L. Sutter-Dallay
Affiliation:
Bordeaux Population Health, INSERM University Department of Adult Psychiatry, Charles-Perrens Hospital, Bordeaux
M. Melchior
Affiliation:
Institut Pierre Louis d’Epidémiologie et de Santé Publique (IPLESP), INSERM Institut Convergences Migration, CNRS, Aubervilliers
B. Heude
Affiliation:
Centre for Research in Epidemiology and Statistics (CRESS), INSERM, Villejuif, France
J. Lepeule
Affiliation:
Institute for Advanced Biosciences (IAB), INSERM, La Tronche
*
*Corresponding author.

Abstract

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Introduction

Behavioral (externalizing) and emotional (internalizing) problems were showed to be associated with the prenatal environment. Changes in placental DNA methylation was identified as a relevant potential mechanism of such association.

Objectives

We aimed to explore the associations between placental DNA methylation and child behavior in order to explore pathways that could link prenatal exposures to child behavior.

Methods

Data including 441 children of 3 years of age from the EDEN mother-child cohort. Child behavior assessed using the Strengths and Difficulties Questionnaire (SDQ). Both hypotheses-driven and exploratory analyses (including epigenome-wide association studies (EWAS) and differentially methylated regions (DMR) analyses) were conducted. The analyses were adjusted for confounding and technical factors and estimated placental cell composition. All the p-values were corrected using a false discovery rate (FDR) procedure for multiple tests.

Results

In the hypothesis-driven analysis, cg26703534 (AHRR), was significantly associated with emotional problems (pFDR = 0.03). In the exploratory analyses, cg09126090 (pFDR = 0.04) and cg10305789 (PPP1R16B; pFDR < 0.01) were significantly associated with peer-relationship problems and 33 DMRs were significantly associated with at least one of the SDQ subscales. Placental DNA methylation showed more associations with internalizing than externalizing symptoms, especially among girls. DMRs tented to include highly methylated CpGs.

Conclusions

This study investigated for the first time the associations between placental DNA methylation and internalizing and externalizing symptoms in preschoolers. Further analyses, such as consortium meta-analyses would be necessary to confirm and extend our results.

Disclosure of Interest

None Declared

Type
Abstract
Information
European Psychiatry , Volume 66 , Special Issue S1: Abstracts of the 31st European Congress of Psychiatry , March 2023 , pp. S532 - S533
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of the European Psychiatric Association
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