Recent efforts to add genetic data to population-based studies have substantially increased our understanding of the interplay of genetic and social environmental factors in shaping health and wellbeing. However, the genetic information found in these studies is typically limited to fixed genetic characteristics (i.e. DNA sequence and its variants). Much less is known about the influence of social environments on variable genetic characteristics such as telomere length (TL) and DNA methylation (DM). This proposal seeks funds to examine levels of and changes in TL and DM among child and adolescent participants in The Fragile Families and Child Wellbeing Study (FFCWS) and to identify early social environmental predictors of these variable genetic characteristics. The FFCWS is uniquely positioned to advance our understanding of the influence of social environments on young children's variable genetic characteristics. The FFCWS has emerged over the past decade as a leading source of information about the social environment and its influence on child health and wellbeing.
Four aims are: 1) To assay TL and DM for children from saliva collected at ages 9 and 15 and to substantially expand the number of fixed DNA markers by reanalyzing 9-year DNA with a custom array (72 genes, 200 SNP variants) that includes genes related to neurodevelopmental, dopaminergic, serotonergic and other behaviorally-relevant pathways. 2) To examine the interaction between the social environment from infancy through early adolescence and: (a) telomere length and changes in telomere length between ages 9 and 15, (b) DNA methylation and changes in DNA methylation between ages 9 and 15, and (c) fixed genetic variants (i.e. SNPs). 3) To examine the influence of the interaction of children's measured genetic differential sensitivity and their social environment on telomere length and DNA methylation. 4) To strengthen the mode experiment in the NICHD funded 15-year FFCWS survey by conducting an additional 250 in-person adolescent interviews. DM and TL will be assayed using saliva samples collected in the year 9 data collection and the year 15 data collection. We expect to find significant changes between ages 9 and 15 in both TL and DM. Some of the change will be due to time and development while other changes are expected to follow the animal model findings that family social environment significantly influences variable genetic traits. With the addition of telomere and methylation data to FFCWS, it will be the only data set currently available to combine: 1) a population-based design, 2) richly detailed longitudinal data on the child since birth, 3) a sample with especially large exposure to harsh environments, 4) DNA markers on important neurotransmitter, neurodevelopmental, and related systems, and 5) telomere length and DNA methylation measures at two time points. Thus data gathered in this study will allow for several new explorations into the interplay of genes, environment, and health. ! !

Public Health Relevance

DNA-based characteristics such as genotype, telomere length (TL) and DNA methylation (DM) are known predictors of health and health behaviors, but little work has been completed on TL and DM in children and adolescents. Further no studies are able to examine social environmental influences on changes in TL and DM in a population- based study. This project investigates changes in TL and DM among children and adolescents, focuses on identifying early social environmental predictors of these variable genetic characteristics, and examines interactions between genotype and the environment!

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
7R01HD076592-02
Application #
8707246
Study Section
Special Emphasis Panel (ZRG1-PSE-K (03))
Program Officer
Bures, Regina M
Project Start
2013-08-01
Project End
2018-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
2
Fiscal Year
2014
Total Cost
$766,913
Indirect Cost
$258,743
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Wiggins, Jillian Lee; Mitchell, Colter; Stringaris, Argyris et al. (2014) Developmental trajectories of irritability and bidirectional associations with maternal depression. J Am Acad Child Adolesc Psychiatry 53:1191-205, 1205.e1-4
Mitchell, Colter; Hobcraft, John; McLanahan, Sara S et al. (2014) Social disadvantage, genetic sensitivity, and children's telomere length. Proc Natl Acad Sci U S A 111:5944-9
Mitchell, Colter; Notterman, Daniel (2014) Reply to Drury and Theall: No evidence of population stratification. Proc Natl Acad Sci U S A 111:E2442