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

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Charlotte A M Cecil1, Esther Walton2, Sara R Jaffee3

  • 1King's College London.

Development and Psychopathology
|June 10, 2017
PubMed

Insights

Epigenetic variations in cord blood DNA methylation are linked to early-onset conduct problems (CP). These DNA methylation patterns, identified at birth, may predict the development of CP in children.

Area of Science:

  • Developmental Psychology
  • Behavioral Genetics
  • Epigenetics

Background:

  • Early-onset conduct problems (CP) predict adult criminality and mental health issues.
  • Both genetic and environmental factors contribute to CP, but underlying biological mechanisms are unclear.
  • Epigenetic modifications, such as DNA methylation, offer a potential link between genes and environment in CP development.

Purpose of the Study:

  • To investigate prospective associations between DNA methylation patterns at birth and the developmental trajectories of conduct problems (CP) from age 4 to 13 years.
  • To identify specific epigenetic markers in cord blood associated with the development of early-onset CP.
  • To explore the relationship between identified methylation sites, prenatal exposures, and genetic factors.

Main Methods:

  • Utilized data from the Avon Longitudinal Study of Parents and Children (ALSPAC).
  • Analyzed DNA methylation in cord blood samples from infants.
  • Examined associations between methylomic variation and conduct problem trajectories (early-onset vs. low CP) using statistical analyses (e.g., false discovery rate < 0.05).

Main Results:

  • Seven genomic loci showed significant methylomic variation differentiating children with early-onset CP from those with low CP.
  • Identified methylation sites were located near genes such as monoglyceride lipase (MGLL), monoamine oxidase A (MAOA), brain-derived neurotrophic factor (BDNF), and FK506 binding protein 5 (FKBP5).
  • Methylation levels at these sites did not predict persistence or desistance of CP behavior within the early-onset group and correlated with prenatal exposures, not known genetic methylation quantitative trait loci.

Conclusions:

  • Specific DNA methylation patterns at birth are associated with the development of early-onset conduct problems.
  • These epigenetic findings provide insights into the biological underpinnings of early-onset CP, potentially mediated by prenatal exposures.
  • Further research can explore the functional roles of identified genes (e.g., MGLL) in the context of conduct problems and neurodevelopment.

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