Associations between placental DNA methylation and emotional and behavioral outcomes in preschoolers: insights from the EDEN Mother-Child Cohort study
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 betwe...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cambridge University Press
2023-03-01
|
| Series: | European Psychiatry |
| Online Access: | https://www.cambridge.org/core/product/identifier/S0924933823011276/type/journal_article |
| _version_ | 1797617175456907264 |
|---|---|
| author | A. Nakamura L. Broseus J. Tost D. Vaiman S. Martins K. Keyes K. Bonello M. Fekom K. Strandberg-Larsen A.-L. Sutter-Dallay M. Melchior B. Heude J. Lepeule |
| author_facet | A. Nakamura L. Broseus J. Tost D. Vaiman S. Martins K. Keyes K. Bonello M. Fekom K. Strandberg-Larsen A.-L. Sutter-Dallay M. Melchior B. Heude J. Lepeule |
| author_sort | A. Nakamura |
| collection | DOAJ |
| description |
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 |
| first_indexed | 2024-03-11T07:52:10Z |
| format | Article |
| id | doaj.art-06067532e0374717a5becb031711948b |
| institution | Directory Open Access Journal |
| issn | 0924-9338 1778-3585 |
| language | English |
| last_indexed | 2024-03-11T07:52:10Z |
| publishDate | 2023-03-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | European Psychiatry |
| spelling | doaj.art-06067532e0374717a5becb031711948b2023-11-17T05:06:26ZengCambridge University PressEuropean Psychiatry0924-93381778-35852023-03-0166S532S53310.1192/j.eurpsy.2023.1127Associations between placental DNA methylation and emotional and behavioral outcomes in preschoolers: insights from the EDEN Mother-Child Cohort studyA. Nakamura0L. Broseus1J. Tost2D. Vaiman3S. Martins4K. Keyes5K. Bonello6M. Fekom7K. Strandberg-Larsen8A.-L. Sutter-Dallay9M. Melchior10B. Heude11J. Lepeule12Institute for Advanced Biosciences (IAB), INSERM, La TroncheInstitute for Advanced Biosciences (IAB), INSERM, La TroncheInstitut de Biologie François Jacob, CEA, EvryGenomics, Epigenetics and Physiopathology of Reproduction, INSERM, Paris, FranceDepartment of Epidemiology, Columbia University Mailman School of Public Health, New York, United StatesDepartment of Epidemiology, Columbia University Mailman School of Public Health, New York, United StatesInstitut Pierre Louis d’Epidémiologie et de Santé Publique (IPLESP), INSERM School of Medicine, Department of general practice, Sorbonne Université, Paris, FranceInstitut Pierre Louis d’Epidémiologie et de Santé Publique (IPLESP), INSERMSection of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, DenmarkBordeaux Population Health, INSERM University Department of Adult Psychiatry, Charles-Perrens Hospital, BordeauxInstitut Pierre Louis d’Epidémiologie et de Santé Publique (IPLESP), INSERM Institut Convergences Migration, CNRS, AubervilliersCentre for Research in Epidemiology and Statistics (CRESS), INSERM, Villejuif, FranceInstitute for Advanced Biosciences (IAB), INSERM, La Tronche 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 Declaredhttps://www.cambridge.org/core/product/identifier/S0924933823011276/type/journal_article |
| spellingShingle | A. Nakamura L. Broseus J. Tost D. Vaiman S. Martins K. Keyes K. Bonello M. Fekom K. Strandberg-Larsen A.-L. Sutter-Dallay M. Melchior B. Heude J. Lepeule Associations between placental DNA methylation and emotional and behavioral outcomes in preschoolers: insights from the EDEN Mother-Child Cohort study European Psychiatry |
| title | Associations between placental DNA methylation and emotional and behavioral outcomes in preschoolers: insights from the EDEN Mother-Child Cohort study |
| title_full | Associations between placental DNA methylation and emotional and behavioral outcomes in preschoolers: insights from the EDEN Mother-Child Cohort study |
| title_fullStr | Associations between placental DNA methylation and emotional and behavioral outcomes in preschoolers: insights from the EDEN Mother-Child Cohort study |
| title_full_unstemmed | Associations between placental DNA methylation and emotional and behavioral outcomes in preschoolers: insights from the EDEN Mother-Child Cohort study |
| title_short | Associations between placental DNA methylation and emotional and behavioral outcomes in preschoolers: insights from the EDEN Mother-Child Cohort study |
| title_sort | associations between placental dna methylation and emotional and behavioral outcomes in preschoolers insights from the eden mother child cohort study |
| url | https://www.cambridge.org/core/product/identifier/S0924933823011276/type/journal_article |
| work_keys_str_mv | AT anakamura associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy AT lbroseus associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy AT jtost associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy AT dvaiman associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy AT smartins associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy AT kkeyes associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy AT kbonello associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy AT mfekom associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy AT kstrandberglarsen associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy AT alsutterdallay associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy AT mmelchior associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy AT bheude associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy AT jlepeule associationsbetweenplacentaldnamethylationandemotionalandbehavioraloutcomesinpreschoolersinsightsfromtheedenmotherchildcohortstudy |