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

TY - JOUR

T1 - Neonatal DNA methylation and early-onset conduct problems: 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 - 2017/6/9

Y1 - 2017/6/9

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 (4-13yrs), using data drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC). Methylomic variation at seven loci across the genome (FDR<0.05) differentiated children who go on to develop early-onset (n = 174¬¬) vs low (n = 86¬¬) CP, including sites in the vicinity of MGLL (involved in endocannabinoid signaling and pain perception). Sub-threshold associations in the vicinity of three candidate genes for CP (MAOA, BDNF, and 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 vs 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 mQTLs. 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 (4-13yrs), using data drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC). Methylomic variation at seven loci across the genome (FDR<0.05) differentiated children who go on to develop early-onset (n = 174¬¬) vs low (n = 86¬¬) CP, including sites in the vicinity of MGLL (involved in endocannabinoid signaling and pain perception). Sub-threshold associations in the vicinity of three candidate genes for CP (MAOA, BDNF, and 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 vs 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 mQTLs. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.

KW - DNA methylation

KW - genome-wide

KW - longitudinal

KW - conduct problems

KW - risk exposure

KW - ALSPAC

UR - http://www.scopus.com/inward/record.url?scp=85020627444&partnerID=8YFLogxK

U2 - 10.1017/S095457941700092X

DO - 10.1017/S095457941700092X

M3 - Article

SN - 0954-5794

SP - 1

EP - 15

JO - Development and Psychopathology

JF - Development and Psychopathology

ER -