Neonatal DNA Methylation and Early-onset Conduct Problems: A Genome-wide, Prospective Study

Overview

Journal Dev Psychopathol

Publisher Cambridge University Press

Specialties Psychiatry
Psychology

Date 2017 Jun 10

PMID 28595673

Citations 14

Authors

Charlotte A M Cecil

Esther Walton

Sara R Jaffee

Tom OConnor

Barbara Maughan

Caroline L Relton

Rebecca G Smith

Wendy McArdle

Tom R Gaunt

Isabelle Ouellet-Morin

Edward D Barker

Affiliations

Soon will be listed here.

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.

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