3-065 - DNA Methylation in a Developmental Context

Session Type: Paper Symposium

Integrative Statement

Exposure to early adverse life events has been linked to a number of psychiatric disorders, including conduct problems (i.e., fighting, lying, stealing). Recent evidence suggests that epigenetic modifications early in life may program biological systems conferring life-long susceptibility to both psychiatric and physical disease. However, most existing birth cohorts were not designed with epigenetics in mind and have not repeatedly collected DNA samples from birth to assess epigenetic changes. Instead, most studies have retrospectively collected DNA and then associated earlier collected measures of risk to this later measure of epigenetic variability.

This symposium consists of three presentations – with innovative analytic strategies – that make of a novel data resource featuring repeated DNA methylation data (n = 339, 50% female; blood samples at birth, age 7, age 9 – Illumina 450k); who follow previously established conduct problem trajectories (and comorbid psychopathologies); and have prenatal and postnatal environmental risk assessments. Paper 1 demonstrates methylation differences between youth with early onset of conduct problems vs. typical developing youth, making use of a repeated measures ANOVA epigenome wide association study (EWAS). Paper 2 shows that the prenatal risk environment associates with the onset and development of conduct problems, via methylation at birth, using an indirect effects-EWAS analysis. Paper 3 applies weighted gene co-expression network analysis to examine patterns of co-methylation underlying the serotonergic, dopaminergic and gaba-ergic systems in relation to risk exposure, conduct problems and common comorbidities.

The papers will be discussed by an expert of gene-environment associations.

Sub Unit

• Developmental Psychopathology

Chair

• Edward D Barker, King's College London

Discussant

• Sara R Jaffee, University of Pennsylvania

Individual Presentations

• Epigenetic Pathways to Conduct Problems - Presenting Author: Rebecca Georgina Smith, King's College London

• Mediating effects of epigenome-wide DNA methylation on the association between prenatal risk and conduct problems in adolescence - Presenting Author: Esther Walton, 10Charge

• DNA co-methylation patterns in neurotransmitter system genes at birth and youth psychiatric symptoms - Presenting Author: Charlotte A. M. Cecil, King's College London