Exome Variants Underlying Weight Gain from Adolescence to Adulthood

This project investigates 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. This study leverages 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 to Adult Health (Add Health), a nationally representative sample of adolescents attending US schools in 1994 with 13 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 researchers 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 is based on GWAS data from the Framingham Heart Study, SNPs with greatest evidence for association with BMI level and change; and literature-based candidates. In the first stage of genotyping, approximately 7,300 SNPs are selected for association testing in a subsample of the Add Health European-American sample. In a second stage, genotypes are assessed on approximately 1,002 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 are identified in each cohort, and then gene by environment interactions are assessed in statistical models predicting BMI over time. This study will further the understanding of how the effects of genetic variation are modified by the environment, a critical step toward development of efficacious programs for the prevention and treatment of obesity and the reduction of disparities in obesity by race/ethnicity and socioeconomic status.

Principal Investigator: Penny Gordon-Larsen

CPC Fellow Investigator: Kathleen Mullan Harris

Other Investigators: Ethan Lange (UNC-CH Dept. of Genetics), Karen L. Mohlke (UNC-CH Dept. of Genetics), Leslie A. Lange (UNC-CH Dept. of Genetics), Caroline Samara Fox (NIH, Ctr. Population Studies), L. Adrienne Cupples (Boston University), Larry Atwood (Boston University)

Funding Source: NIH NICHD

Grant Number: R01HD057194

Funding Period: 1/1/2008 - 6/30/2019

Primary Research Area: Population Health

Affiliated Research Projects:

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