Abstract
Low prosocial behavior in childhood has been consistently linked to later psychopathology, with evidence supporting the influence of both genetic and environmental factors on its development. Although neonatal DNA methylation (DNAm) has been found to prospectively associate with a range of psychological traits in childhood, its potential role in prosocial development has yet to be investigated. This study investigated prospective associations between cord blood DNAm at birth and low prosocial behavior within and across four longitudinal birth cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. We examined (a) developmental trajectories of "chronic-low" versus "typical" prosocial behavior across childhood in a case-control design (N = 2,095), and (b) continuous "low prosocial" scores at comparable cross-cohort time-points (N = 2,121). Meta-analyses were performed to examine differentially methylated positions and regions. At the cohort-specific level, three CpGs were found to associate with chronic low prosocial behavior; however, none of these associations was replicated in another cohort. Meta-analysis revealed no epigenome-wide significant CpGs or regions. Overall, we found no evidence for associations between DNAm patterns at birth and low prosocial behavior across childhood. Findings highlight the importance of employing multi-cohort approaches to replicate epigenetic associations and reduce the risk of false positive discoveries.
Original language | English |
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Pages (from-to) | 228-241 |
Number of pages | 14 |
Journal | American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics |
Volume | 186 |
Issue number | 4 |
Early online date | 25 Jun 2021 |
DOIs | |
Publication status | Published - Jun 2021 |
Bibliographical note
© 2021 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.Funding
The UK Medical Research Council (MRC) and Wellcome Trust (102215/2/13/2) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ). Analysis of ALSPAC data was funded by the UK Economic and Social Research Council (ESRC; ES/N000498/1). ARIES was funded by the Biotechnology and Biological Sciences Research Council (BBSRC; BBI025751/1 and BB/I025263/1). Supplementary funding to generate DNA methylation data which are (or will be) included in ARIES has been obtained from the MRC, ESRC, National Institutes of Health, and other sources. ARIES is maintained under the auspices of the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_00011/4 and MC_UU_00011/5). The ALSPAC methylation component of this article was supported by a Eunice Kennedy Shriver National Institute of Child and Human Development grant to EDB (R01HD068437) with further funding from the ESRC (ES/R005516/1). AJM was supported by the ESRC (ES/J500057/1) and National University of Ireland. This publication is the work of the authors, and EDB and CAMC serve as guarantors for the contents of this article. Core funding for the LINA study is provided by the Helmholtz Center for Environmental Research—UFZ / Department of Environmental Immunology, with methylation analysis supported by the German Cancer Research Centre—DKFZ. LINA: The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center Rotterdam, Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development and the Ministry of Health, Welfare and Sport. The EWAS data was funded by a grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA; project nr. 050‐060‐810), funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and a grant from the National Institute of Child and Human Development (R01HD068437). This project received funding from the European Union's Horizon 2020 research and innovation program (733,206, LifeCycle; 848,158, EarlyCause) and from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no.529051022 and PREcisE project no. P75416). CAMC has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska‐Curie grant agreement No 707404. CAMC and EW are supported by grant agreement No 848158 (EarlyCause). ML is supported by the scholarship from the China Scholarship Council (201706990036). MHvIJ and MJB‐K are supported by the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development). MJB‐K was supported by the European Research Council (ERC AdG 669,249). MHvIJ and APCH are also supported by a Spinoza Award of the Netherlands Organization for Scientific Research to MHvIJ. The epigenetic studies in INMA were mainly funded by grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, CP18/00018), Spanish Ministry of Health (FIS‐PI04/1436, FIS‐PI08/1151 including FEDER funds, FIS‐PI11/00610, FIS‐FEDER‐PI06/0867, FIS‐FEDER‐PI03‐1615), Generalitat de Catalunya‐CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430), EU Commission (261357‐MeDALL: Mechanisms of the Development of ALLergy), and European Research Council (268479‐BREATHE: BRain dEvelopment and Air polluTion ultrafine particles in scHool childrEn). MCT is funded by a Juan de la Cierva—Formación Postdoctoral Contract awarded by Ministry of Science and Innovation (FJC2018‐036335‐I). The 4, 7, and 11 year follow‐up visits was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds; PI15/00118 incl. FEDER funds; CP16/00128 incl. FEDER funds; PI16/00118 incl. FEDER funds; PI16/00261 incl. FEDER funds; PI18/00547 incl. FEDER funds), CIBERESP, Generalitat de Catalunya‐CIRIT 1999SGR 00241, Generalitat de Catalunya‐AGAUR (2009 SGR 501, 2014 SGR 822), Fundació La marató de TV3 (090430), Spanish Ministry of Economy and Competitiveness (SAF2012‐32991 incl. FEDER funds), Agence Nationale de Securite Sanitaire de l'Alimentation de l'Environnement et du Travail (1262C0010; EST‐2016 RF‐21), EU Commission (261357, 308333, 603794 and 634453). We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019‐2023” Program (CEX2018‐000806‐S), and support from the Generalitat de Catalunya through the CERCA Program. INMA: Agence Nationale de Securite Sanitaire de l'Alimentation de l'Environnement et du Travail, Grant/Award Number: 1262C0010; Agència de Gestió d'Ajuts Universitaris i de Recerca, Grant/Award Numbers: 2009 SGR 501, 2014 SGR 822; China Scholarship Council, Grant/Award Number: 201706990036; Comissió Interdepartamental de Recerca i Innovació Tecnològica, Grant/Award Number: 1999SGR 00241; Deutsches Krebsforschungszentrum; Economic and Social Research Council, Grant/Award Numbers: ES/J500057/1, ES/R005516/1; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Grant/Award Number: R01HD068437; European Commission, Grant/Award Numbers: 261357, 308333, 603794, 634453; Fundació la Marató de TV3, Grant/Award Number: 090430; H2020 European Research Council, Grant/Award Numbers: 268479, 669249; H2020 Marie Skłodowska‐Curie Actions, Grant/Award Numbers: 707404, 848158; Helmholtz‐Zentrum für Umweltforschung; Instituto de Salud Carlos III, Grant/Award Numbers: CB06/02/0041, CP13/00054, CP16/00128, CP18/00018, G03/176, PI041436, PI081151, PI12/01890, PI15/00118, PI16/00118, PI16/00261, PI18/00547; Medical Research Council, Grant/Award Number: MC_UU_00011/5; Ministerio de Ciencia e Innovación, Grant/Award Number: FJC2018‐036335‐I; National University of Ireland; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: 024‐001‐003, 050‐060‐810; Spanish Ministry of Economy and Competitiveness, Grant/Award Number: SAF2012‐32991; Spanish Ministry of Health, Grant/Award Numbers: FIS‐FEDER‐PI03‐1615, FIS‐FEDER‐PI06/0867, FIS‐PI04/1436, FIS‐PI08/1151, FIS‐PI11/00610 Funding information
Funders | Funder number |
---|---|
CIBERESP | |
Centro de Excelencia Severo Ochoa 2019‐2023 | |
Erasmus Medical Center Rotterdam | |
Generalitat de Catalunya‐AGAUR | |
Generalitat de Catalunya‐CIRIT | |
Helmholtz Center for Environmental Research | |
Netherlands Consortium for Healthy Aging | |
Netherlands Genomics Initiative | |
Netherlands Organization for Health Research and Development | |
Spanish Ministry of Health | FIS‐PI04/1436, FIS‐PI11/00610, FIS‐PI08/1151, FIS‐FEDER‐PI03‐1615, FIS‐FEDER‐PI06/0867 |
Spanish Ministry of Science and Innovation and State Research Agency | |
National Institute of Child Health and Human Development | R01HD068437 |
Deutsches Krebsforschungszentrum | |
Fundació la Marató de TV3 | 090430 |
Eunice Kennedy Shriver National Institute of Child Health and Human Development | |
National University of Ireland | |
H2020 European Research Council | 268479, 669249 |
H2020 Marie Skłodowska-Curie Actions | 707404 |
Joint Programming Initiative on Antimicrobial Resistance | |
Medical Research Council | MC_UU_00011/5 |
Biotechnology and Biological Sciences Research Council | BBI025751/1, BB/I025263/1 |
Economic and Social Research Council | ES/J500057/1, ES/N000498/1, ES/R005516/1 |
European Commission | 634453, 261357, 603794, 308333 |
European Research Council | |
Economic Development Board - Singapore | |
Ministry of Education, Culture, Sports, Science and Technology | 024.001.003 |
ZonMw | 529051022, P75416, 848158 |
Erasmus Universiteit Rotterdam | |
Generalitat de Catalunya | |
Ministerie van Volksgezondheid, Welzijn en Sport | |
Agència de Gestió d'Ajuts Universitaris i de Recerca | 2009 SGR 501, 2014 SGR 822 |
Erasmus Medisch Centrum | |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | 024‐001‐003, 050‐060‐810 |
Ministerio de Economía y Competitividad | SAF2012‐32991 |
China Scholarship Council | 201706990036 |
Instituto de Salud Carlos III | PI041436, PI081151, PI16/00118, CB06/02/0041, G03/176, CP13/00054, CP16/00128, PI12/01890, PI15/00118, PI16/00261, PI18/00547, CP18/00018, INMA G03/176 |
Helmholtz-Zentrum für Umweltforschung | |
Ministerio de Ciencia e Innovación | FJC2018‐036335‐I |
Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail | EST‐2016 RF‐21, 1262C0010 |
Horizon 2020 | 733,206 |
Comissió Interdepartamental de Recerca i Innovació Tecnològica | 1999SGR 00241 |
Keywords
- Adolescent
- Altruism
- Birth Cohort
- Case-Control Studies
- Child
- Child, Preschool
- Cohort Studies
- Cordocentesis/methods
- CpG Islands/genetics
- DNA Methylation/genetics
- Epigenesis, Genetic/genetics
- Epigenome/genetics
- Epigenomics/methods
- Female
- Fetal Blood/metabolism
- Genome-Wide Association Study/methods
- Humans
- Infant, Newborn/metabolism
- Male