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.

Public Health Relevance

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 #
5R01HD057194-04
Application #
8098750
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Raiten, Daniel J
Project Start
2008-09-30
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
4
Fiscal Year
2011
Total Cost
$563,415
Indirect Cost
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
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Marouli, Eirini (see original citation for additional authors) (2017) Rare and low-frequency coding variants alter human adult height. Nature 542:186-190
Fernández-Rhodes, Lindsay; Gong, Jian; Haessler, Jeffrey et al. (2017) Trans-ethnic fine-mapping of genetic loci for body mass index in the diverse ancestral populations of the Population Architecture using Genomics and Epidemiology (PAGE) Study reveals evidence for multiple signals at established loci. Hum Genet 136:771-800
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Justice, Anne E (see original citation for additional authors) (2017) Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat Commun 8:14977
Young, K L; Graff, M; North, K E et al. (2016) Influence of SNP*SNP interaction on BMI in European American adolescents: findings from the National Longitudinal Study of Adolescent Health. Pediatr Obes 11:95-101
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Lange, Leslie A; Graff, Mariaelisa; Lange, Ethan M et al. (2016) Evidence for Association between SH2B1 Gene Variants and Glycated Hemoglobin in Nondiabetic European American Young Adults: The Add Health Study. Ann Hum Genet 80:294-305
Graff, M; Richardson, A S; Young, K L et al. (2016) The interaction between physical activity and obesity gene variants in association with BMI: Does the obesogenic environment matter? Health Place 42:159-165
Surendran, Praveen (see original citation for additional authors) (2016) Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Nat Genet 48:1151-1161

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