Neonatal DNA methylation and early-onset conduct problems: A genome-wide prospective study

Charlotte A.M. Cecil, Esther Walton, Sara R. Jaffee, Tom O'Connor, Barbara Maughan, Caroline L. Relton, Rebecca G. Smith, Wendy McArdle, Tom R. Gaunt, Isabelle Ouellet-Morin, Edward D. Barker

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4-13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate <0.05) differentiated children who go on to develop early-onset (n = 174) versus low (n = 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.
Original languageEnglish
Pages (from-to)383-397
Number of pages15
JournalDevelopment and Psychopathology
Volume20
Issue number2
Early online date9 Jun 2017
DOIs
Publication statusPublished - 31 May 2018

Keywords

  • DNA Methylation
  • genome-wide
  • ALSPAC
  • conduct problems
  • risk exposure

Cite this

Cecil, C. A. M., Walton, E., Jaffee, S. R., O'Connor, T., Maughan, B., Relton, C. L., ... Barker, E. D. (2018). Neonatal DNA methylation and early-onset conduct problems: A genome-wide prospective study. Development and Psychopathology, 20(2), 383-397. https://doi.org/10.1017/S095457941700092X

Neonatal DNA methylation and early-onset conduct problems : A genome-wide prospective study. / Cecil, Charlotte A.M.; Walton, Esther; Jaffee, Sara R.; O'Connor, Tom; Maughan, Barbara; Relton, Caroline L.; Smith, Rebecca G.; McArdle, Wendy; Gaunt, Tom R.; Ouellet-Morin, Isabelle; Barker, Edward D.

In: Development and Psychopathology, Vol. 20, No. 2, 31.05.2018, p. 383-397.

Research output: Contribution to journalArticle

Cecil, CAM, Walton, E, Jaffee, SR, O'Connor, T, Maughan, B, Relton, CL, Smith, RG, McArdle, W, Gaunt, TR, Ouellet-Morin, I & Barker, ED 2018, 'Neonatal DNA methylation and early-onset conduct problems: A genome-wide prospective study', Development and Psychopathology, vol. 20, no. 2, pp. 383-397. https://doi.org/10.1017/S095457941700092X
Cecil, Charlotte A.M. ; Walton, Esther ; Jaffee, Sara R. ; O'Connor, Tom ; Maughan, Barbara ; Relton, Caroline L. ; Smith, Rebecca G. ; McArdle, Wendy ; Gaunt, Tom R. ; Ouellet-Morin, Isabelle ; Barker, Edward D. / Neonatal DNA methylation and early-onset conduct problems : A genome-wide prospective study. In: Development and Psychopathology. 2018 ; Vol. 20, No. 2. pp. 383-397.
@article{bf3a28e4583544469a9fd35f45d80d1e,
title = "Neonatal DNA methylation and early-onset conduct problems: A genome-wide prospective study",
abstract = "Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4-13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate <0.05) differentiated children who go on to develop early-onset (n = 174) versus low (n = 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.",
keywords = "DNA Methylation, genome-wide, ALSPAC, conduct problems, risk exposure",
author = "Cecil, {Charlotte A.M.} and Esther Walton and Jaffee, {Sara R.} and Tom O'Connor and Barbara Maughan and Relton, {Caroline L.} and Smith, {Rebecca G.} and Wendy McArdle and Gaunt, {Tom R.} and Isabelle Ouellet-Morin and Barker, {Edward D.}",
year = "2018",
month = "5",
day = "31",
doi = "10.1017/S095457941700092X",
language = "English",
volume = "20",
pages = "383--397",
journal = "Development and Psychopathology",
issn = "1469-2198",
publisher = "Cambridge University Press",
number = "2",

}

TY - JOUR

T1 - Neonatal DNA methylation and early-onset conduct problems

T2 - A genome-wide prospective study

AU - Cecil, Charlotte A.M.

AU - Walton, Esther

AU - Jaffee, Sara R.

AU - O'Connor, Tom

AU - Maughan, Barbara

AU - Relton, Caroline L.

AU - Smith, Rebecca G.

AU - McArdle, Wendy

AU - Gaunt, Tom R.

AU - Ouellet-Morin, Isabelle

AU - Barker, Edward D.

PY - 2018/5/31

Y1 - 2018/5/31

N2 - Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4-13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate <0.05) differentiated children who go on to develop early-onset (n = 174) versus low (n = 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.

AB - Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4-13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate <0.05) differentiated children who go on to develop early-onset (n = 174) versus low (n = 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.

KW - DNA Methylation

KW - genome-wide

KW - ALSPAC

KW - conduct problems

KW - risk exposure

U2 - 10.1017/S095457941700092X

DO - 10.1017/S095457941700092X

M3 - Article

VL - 20

SP - 383

EP - 397

JO - Development and Psychopathology

JF - Development and Psychopathology

SN - 1469-2198

IS - 2

ER -