Neonatal DNA methylation and childhood low prosocial behavior: An epigenome-wide association meta-analysis

Mannan Luo; Alan J. Meehan; Esther Walton; Stefan Röder; Gunda Herberth; Ana C. Zenclussen; Marta Cosín-Tomás; Jordi Sunyer; Rosa H. Mulder; Andrea P. Cortes Hidalgo; Marian J. Bakermans-Kranenburg; Janine F. Felix; Caroline Relton; Matthew Suderman; Irene Pappa; Rianne Kok; Henning Tiemeier; Marinus H. van IJzendoorn; Edward D. Barker; Charlotte A.M. Cecil

doi:10.1002/ajmg.b.32862

Neonatal DNA methylation and childhood low prosocial behavior: An epigenome-wide association meta-analysis

Mannan Luo, Alan J. Meehan, Esther Walton, Stefan Röder, Gunda Herberth, Ana C. Zenclussen, Marta Cosín-Tomás, Jordi Sunyer, Rosa H. Mulder, Andrea P. Cortes Hidalgo, Marian J. Bakermans-Kranenburg, Janine F. Felix, Caroline Relton, Matthew Suderman, Irene Pappa, Rianne Kok, Henning Tiemeier, Marinus H. van IJzendoorn, Edward D. Barker, Charlotte A.M. Cecil^*

^*Corresponding author for this work

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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
Pages (from-to)	228-241
Number of pages	14
Journal	American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume	186
Issue number	4
DOIs	https://doi.org/10.1002/ajmg.b.32862
Publication status	Published - 25 Jun 2021

Bibliographical note

Funding information: 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

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© 2021 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.

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Luo, M., Meehan, A. J., Walton, E., Röder, S., Herberth, G., Zenclussen, A. C., Cosín-Tomás, M., Sunyer, J., Mulder, R. H., Cortes Hidalgo, A. P., Bakermans-Kranenburg, M. J., Felix, J. F., Relton, C., Suderman, M., Pappa, I., Kok, R., Tiemeier, H., van IJzendoorn, M. H., Barker, E. D., & Cecil, C. A. M. (2021). Neonatal DNA methylation and childhood low prosocial behavior: An epigenome-wide association meta-analysis. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 186(4), 228-241. https://doi.org/10.1002/ajmg.b.32862

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title = "Neonatal DNA methylation and childhood low prosocial behavior: An epigenome-wide association meta-analysis",

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.",

author = "Mannan Luo and Meehan, {Alan J.} and Esther Walton and Stefan R{\"o}der and Gunda Herberth and Zenclussen, {Ana C.} and Marta Cos{\'i}n-Tom{\'a}s and Jordi Sunyer and Mulder, {Rosa H.} and {Cortes Hidalgo}, {Andrea P.} and Bakermans-Kranenburg, {Marian J.} and Felix, {Janine F.} and Caroline Relton and Matthew Suderman and Irene Pappa and Rianne Kok and Henning Tiemeier and {van IJzendoorn}, {Marinus H.} and Barker, {Edward D.} and Cecil, {Charlotte A.M.}",

note = "Funding information: Agence Nationale de Securite Sanitaire de l'Alimentation de l'Environnement et du Travail, Grant/Award Number: 1262C0010; Ag{\`e}ncia de Gesti{\'o} d'Ajuts Universitaris i de Recerca, Grant/Award Numbers: 2009 SGR 501, 2014 SGR 822; China Scholarship Council, Grant/Award Number: 201706990036; Comissi{\'o} Interdepartamental de Recerca i Innovaci{\'o} Tecnol{\`o}gica, 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; Fundaci{\'o} la Marat{\'o} de TV3, Grant/Award Number: 090430; H2020 European Research Council, Grant/Award Numbers: 268479, 669249; H2020 Marie Sk{\l}odowska-Curie Actions, Grant/Award Numbers: 707404, 848158; Helmholtz-Zentrum f{\"u}r 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 Innovaci{\'o}n, 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 Publisher Copyright: {\textcopyright} 2021 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.",

year = "2021",

month = jun,

day = "25",

doi = "10.1002/ajmg.b.32862",

language = "English",

volume = "186",

pages = "228--241",

journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",

issn = "1552-4841",

publisher = "Wiley-Liss Inc.",

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Luo, M, Meehan, AJ, Walton, E, Röder, S, Herberth, G, Zenclussen, AC, Cosín-Tomás, M, Sunyer, J, Mulder, RH , Cortes Hidalgo, AP, Bakermans-Kranenburg, MJ, Felix, JF, Relton, C, Suderman, M, Pappa, I , Kok, R , Tiemeier, H , van IJzendoorn, MH, Barker, ED & Cecil, CAM 2021, 'Neonatal DNA methylation and childhood low prosocial behavior: An epigenome-wide association meta-analysis', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 186, no. 4, pp. 228-241. https://doi.org/10.1002/ajmg.b.32862

TY - JOUR

T1 - Neonatal DNA methylation and childhood low prosocial behavior

T2 - An epigenome-wide association meta-analysis

AU - Luo, Mannan

AU - Meehan, Alan J.

AU - Walton, Esther

AU - Röder, Stefan

AU - Herberth, Gunda

AU - Zenclussen, Ana C.

AU - Cosín-Tomás, Marta

AU - Sunyer, Jordi

AU - Mulder, Rosa H.

AU - Cortes Hidalgo, Andrea P.

AU - Bakermans-Kranenburg, Marian J.

AU - Felix, Janine F.

AU - Relton, Caroline

AU - Suderman, Matthew

AU - Pappa, Irene

AU - Kok, Rianne

AU - Tiemeier, Henning

AU - van IJzendoorn, Marinus H.

AU - Barker, Edward D.

AU - Cecil, Charlotte A.M.

N1 - Funding information: 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 Publisher Copyright: © 2021 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.

PY - 2021/6/25

Y1 - 2021/6/25

N2 - 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.

AB - 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.

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U2 - 10.1002/ajmg.b.32862

DO - 10.1002/ajmg.b.32862

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JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

SN - 1552-4841

IS - 4

ER -

Neonatal DNA methylation and childhood low prosocial behavior: An epigenome-wide association meta-analysis

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