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

Published online by Cambridge University Press:  09 June 2017

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  and
Isabelle Ouellet-Morin
...Show all authors
Charlotte A. M. Cecil*
Affiliation:
King's College London
Esther Walton
Affiliation:
University of Bristol
Sara R. Jaffee
Affiliation:
University of Pennsylvania
Tom O'Connor
Affiliation:
University of Rochester Medical Center
Barbara Maughan
Affiliation:
King's College London
Caroline L. Relton
Affiliation:
University of Bristol
Rebecca G. Smith
Affiliation:
Exeter University
Wendy McArdle
Affiliation:
University of Bristol
Tom R. Gaunt
Affiliation:
University of Bristol
Isabelle Ouellet-Morin
Affiliation:
University of Montreal
Edward D. Barker*
Affiliation:
King's College London
*
Address correspondence and preprint requests to: Charlotte A. M. Cecil or Edward D. Barker, Department of Psychology, King's College London, Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, London, UK SE5 8AF; E-mail: charlotte.cecil@kcl.ac.uk or ted.barker@kcl.ac.uk.
Address correspondence and preprint requests to: Charlotte A. M. Cecil or Edward D. Barker, Department of Psychology, King's College London, Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, London, UK SE5 8AF; E-mail: charlotte.cecil@kcl.ac.uk or ted.barker@kcl.ac.uk.
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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.

Type
Regular Articles
Information
Development and Psychopathology , Volume 30 , Issue 2 , May 2018 , pp. 383 - 397
Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole Avon Longitudinal Study of Parents and Children (ALSPAC) team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. We thank all involved with the ALSPAC DNA methylation, particularly the laboratory scientists and bioinformaticians who contributed considerable time and expertise to the data in this paper. The UK Medical Research Council and the Wellcome Trust (Grant 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors, who will serve as guarantors for the contents of this paper. This research was specifically supported by National Institute of Child and Human Development Grant R01HD068437 (to E.D.B.). The first author (C.A.M.C.) is supported by Economic and Social Research Council Grant ES/N001273/1.

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