The methylomic consequences of neighborhood disadvantage for youth risk-taking behaviors.

ABSTRACT
Neighborhood disadvantage is a potent predictor of youth risk-taking and aggressive antisocial
behaviors (ASB). This association with youth ASB emerges early in life and increases over time.
Understanding how neighborhood disadvantage leads to youth ASB thus constitutes a critical public
health need. To date, however, the biological mechanism(s) through which disadvantage influences
youth ASB remain unclear. The proposed R01 will explore methylation as a key biological pathway
underlying the association between neighborhood disadvantage and youth ASB. We specifically
postulate that neighborhood disadvantage and its social and physical `active ingredients' (e.g., harsh
parenting, exposure to community violence, and toxicant exposure) will predict youth ASB via
methylomic alterations, and that these associations will persist over any genetic confounds. To
examine this possibility, we will generate methylation data from blood and/or saliva at four
assessment waves (neonatal, middle childhood, and early and mid-adolescence) in a discovery
sample of 500 adolescent twin pairs (1,000 twins) residing in modestly-to-severely disadvantaged
neighborhoods. We then propose to replicate the phenotypic associations in an independent sample
of 237 singleton youth living in poverty with methylation data from blood and/or saliva at three
assessment waves (neonatal, middle childhood, and mid-adolescence). As our final step, we will
leverage the focus on twin pairs in our Discovery twin sample to evaluate whether the replicated
methylomic associations are environmental and/or genetic in origin. In short, the proposed R01 will
not only identify neighborhood-induced methylomic alterations in two independent samples of
impoverished youth, but will also illuminate the environmental and/or genetic etiology of those
replicated alterations. In this way, we will move the field of social and environmental epigenetics
forward in several areas.

Grant Number: 5R01HD104297-05
NIH Institute/Center: NIH
Principal Investigator: S. Alexandra Burt