Obesity is an important risk factor for many aging-related conditions such as type 2 diabetes, cardiovascular disease, cancer, injuries, physical function disabilities, and premature mortality. Obesity risk can be established early in the life course. Socioeconomic disadvantage and other forms of social adversity occurring prenatally and during early childhood substantially increase risk for obesity in adulthood. This has profound implications for efforts to reduce morbidity associated with obesity-related conditions. A major unresolved question is whether or not obesity risk initiated in childhood can be altered by interventions in adulthood. If so, then it is critical to identify modifiable intervention targes. Modifiable intervention targets are by definition factors that lie along the causal pathway linking early life adversity to obesity in adulthood (i.e. that mediate the link between risk and disease). To expand knowledge of etiology, all such mediators are of interest. For public health purposes, we are most interested in mediators with the strongest effects, as intervening on these mediators will provide the most impact in the effort to reverse the long-term effects of early adversity on adulthood obesity. There is surprisingly little known about whether major candidate factors such as diet, physical activity, smoking, depression, education and epigenetic methylation patterns mediate the links between early life adversity and adulthood obesity. Consequently, we propose the following specific aims, focusing on two primary clinically relevant measures of adiposity in adulthood, specifically body mass index and waist circumference: (1) To investigate the roles of socioeconomic, behavioral, and mental health factors in the associations between childhood economic disadvantage, social adversity and adult adiposity. (2) To determine if there are epigenetic DNA methylation mediators of the associations of childhood economic disadvantage and social adversity with mid-life adiposity. The proposed aims will be achieved using unique data and biosamples from the New England Family Study, a long-term follow-up study of births from the Providence, RI and Boston, MA cohorts of the Collaborative Perinatal Project, born between1959-1966. There are few prenatal cohorts in the world with directly assessed social exposures from pregnancy through the first 7 years of life. We propose to perform Infinium HumanMethylation450 BeadChip DNA methylation arrays on stored adipose and leukocyte samples for a sample of 68 males and 68 females with epigenetic profiles. Cardiovascular and other demographic variables were directly assessed in 831 participants during the years 2005-2011 at age range 42- 50 years. We will employ sophisticated causal mediation analyses to estimate the comparative effects of the conditions we hypothesize to be potential intervention targets. The results of the proposed study will provide new etiologic insights regarding the pathways linking early adversity to obesity in adulthood, and will provide evidence regarding the anticipated benefits of interventions on a wide range of potential targets to reduce the long-term consequences of early childhood adversity on obesity.

Public Health Relevance

Obesity is an important risk factor for many aging-related conditions such as type 2 diabetes, cardiovascular disease, cancer, injuries, physical function disabilities and premature mortality. Socioeconomic disadvantage and other forms of social adversity occurring prenatally and during early childhood substantially increase risk for obesity in adulthood. The results of the proposed study will provide evidence on the pathways (e.g. diet, physical activity, smoking, education and depressive symptomatology) linking early life adversity to obesity in adulthood, which in turn will inform knowledge about anticipated benefits of adulthood interventions on these pathways to reduce the long-term consequences of early childhood adversity on obesity.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01AG048825-01
Application #
8796955
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Haaga, John G
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Brown University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
City
Providence
State
RI
Country
United States
Zip Code
02912
Loucks, Eric B; Britton, Willoughby B; Howe, Chanelle J et al. (2016) Associations of Dispositional Mindfulness with Obesity and Central Adiposity: the New England Family Study. Int J Behav Med 23:224-33
Loucks, Eric B; Gilman, Stephen E; Britton, Willoughby B et al. (2016) Associations of Mindfulness with Glucose Regulation and Diabetes. Am J Health Behav 40:258-67
Huang, Yen-Tsung; Yang, Hwai-I; Liu, Jessica et al. (2016) Mediation Analysis of Hepatitis B and C in Relation to Hepatocellular Carcinoma Risk. Epidemiology 27:14-20
Loucks, Eric B; Gilman, Stephen E; Howe, Chanelle J et al. (2015) Education and coronary heart disease risk: potential mechanisms such as literacy, perceived constraints, and depressive symptoms. Health Educ Behav 42:370-9
Loucks, Eric B; Britton, Willoughby B; Howe, Chanelle J et al. (2015) Positive Associations of Dispositional Mindfulness with Cardiovascular Health: the New England Family Study. Int J Behav Med 22:540-50
Stinson, Lynda J; Stroud, Laura R; Buka, Stephen L et al. (2015) Prospective evaluation of associations between prenatal cortisol and adulthood coronary heart disease risk: the New England family study. Psychosom Med 77:237-45
Huang, Yen-Tsung; Hsu, Thomas; Kelsey, Karl T et al. (2015) Integrative analysis of micro-RNA, gene expression, and survival of glioblastoma multiforme. Genet Epidemiol 39:134-43
Agha, Golareh; Houseman, E Andres; Kelsey, Karl T et al. (2015) Adiposity is associated with DNA methylation profile in adipose tissue. Int J Epidemiol 44:1277-87
Huang, Yen-Tsung (2015) Integrative modeling of multi-platform genomic data under the framework of mediation analysis. Stat Med 34:162-78
Su, Shaoyong; Jimenez, Marcia P; Roberts, Cole T F et al. (2015) The role of adverse childhood experiences in cardiovascular disease risk: a review with emphasis on plausible mechanisms. Curr Cardiol Rep 17:88