The objective of the proposed research is to investigate how genes, environment, and gene-environment interactions influence temporal changes in body mass index (BMI) at vulnerable periods of the life cycle. Little is known about how individual susceptibility to environmental contexts influences attained size and trajectories of body mass change. We will leverage Framingham Heart Study genome-wide association study (GWAS) data to investigate interactions between genetic variation and modifiable environmental factors in the determination of body mass in two NIH-funded longitudinal cohort studies with high obesity incidence: The National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents attending US schools in 1994 with 12 years of follow-up, including 5,000 European Americans, 2,100 African Americans, 1,500 Hispanic Americans and 900 Asian Americans;and the Cebu Longitudinal Health and Nutrition Survey (CLHNS), a cohort of 1,800 reproductive aged women with 20 years of follow up, which we will use to augment the Asian sample and to compare results across different environments. Both datasets provide detailed longitudinal data at individual, household, and community levels and sufficient DNA for extensive genotyping. Single nucleotide polymorphisms (SNP) selection will be based on: 1) GWAS data from the Framingham Heart Study, SNPs with greatest evidence for association with BMI level and change; and 2) literature-based candidates. In the first stage of genotyping, we will select approximately 7,300 SNPs for association testing in a subsample of the Add Health European-American sample. In a second stage, we will genotype approximately 1,200 of the most strongly associated SNPs from stage 1 in the rest of the European, African, Hispanic, and Asian American Add Health subsamples and in the CLHNS sample. Environmental factors, behaviors and genes that predict BMI level and change will be identified in each cohort, and then gene by environment interactions will be assessed in statistical models predicting BMI over time. Our study will further the understanding of how the effects of genetic variation are modified by the environment, a critical step towards development of efficacious programs for the prevention and treatment of obesity and the reduction of disparities in obesity by race/ethnicity and socioeconomic status. PROPOSAL NARRATIVE The objective of the proposed research is to investigate how genes, environment, and gene-environment interactions influence temporal changes in body mass index (BMI) at vulnerable periods of the life cycle. Our study will further the understanding of how the effects of genetic variation are modified by the environment, a critical step towards development of efficacious programs for the prevention and treatment of obesity and the reduction of disparities in obesity by race/ethnicity and socioeconomic status.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD057194-05
Application #
8304391
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Raiten, Daniel J
Project Start
2008-09-30
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$547,518
Indirect Cost
$177,574
Name
University of North Carolina Chapel Hill
Department
Nutrition
Type
Schools of Public Health
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Richardson, A S; Dietz, W H; Gordon-Larsen, P (2014) The association between childhood sexual and physical abuse with incident adult severe obesity across 13?years of the National Longitudinal Study of Adolescent Health. Pediatr Obes 9:351-61
Albrecht, Sandra S; Gordon-Larsen, Penny (2014) Socioeconomic gradients in body mass index (BMI) in US immigrants during the transition to adulthood: examining the roles of parental education and intergenerational educational mobility. J Epidemiol Community Health 68:842-8
Gray, Christine L; Robinson, Whitney R (2014) Throwing out the baby with the bathwater?: Comparing 2 approaches to implausible values of change in body size. Epidemiology 25:591-4
Richardson, A S; North, K E; Graff, M et al. (2014) Moderate to vigorous physical activity interactions with genetic variants and body mass index in a large US ethnically diverse cohort. Pediatr Obes 9:e35-46
Graff, Mariaelisa; Ngwa, Julius S; Workalemahu, Tsegaselassie et al. (2013) Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course. Hum Mol Genet 22:3597-607
Graff, M; North, K E; Richardson, A S et al. (2013) Screen time behaviours may interact with obesity genes, independent of physical activity, to influence adolescent BMI in an ethnically diverse cohort. Pediatr Obes 8:e74-9
Graff, M; North, K E; Franceschini, N et al. (2013) PNPLA3 gene-by-visceral adipose tissue volume interaction and the pathogenesis of fatty liver disease: the NHLBI family heart study. Int J Obes (Lond) 37:432-8
Attard, Samantha M; Herring, Amy H; Howard, Annie Green et al. (2013) Longitudinal trajectories of BMI and cardiovascular disease risk: the national longitudinal study of adolescent health. Obesity (Silver Spring) 21:2180-8
The, Natalie S; Richardson, Andrea S; Gordon-Larsen, Penny (2013) Timing and duration of obesity in relation to diabetes: findings from an ethnically diverse, nationally representative sample. Diabetes Care 36:865-72
Albrecht, Sandra S; Gordon-Larsen, Penny (2013) Ethnic differences in body mass index trajectories from adolescence to adulthood: a focus on Hispanic and Asian subgroups in the United States. PLoS One 8:e72983

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