Evidence from biometric and molecular studies indicates that genetic factors significantly influence body mass among humans. This has led to recent efforts to identify single nucleotide polymorphisms (SNPs) across to the entire human genome that are associated with adult and adolescent weight. However, all existing genome wide association (GWA) studies of body mass and obesity have focused on main genetic effects rather than interaction effects between genetic and environmental factors. This leads to gene-environment interaction (GxE) studies that focus on environmental factors that moderate genetic main effects. In the event that there are only genetic effects within particular environments (e.g., no main genetic effects), then current GWA models will overlook important genetic influences. Because body mass is strongly influenced by social environmental factors and because genetic associations for body mass are contingent upon social- environmental influences, environmental risk (and protective) factors must be included in the conceptual understandings and methodological approaches to GWA. While GxE studies involving a single genetic variant are increasingly common, no existing work has specifically focused on genome-wide approaches to GxE. Our approach is a fundamentally new way of examining genetic influences on body mass that extends established GWA methods and draws upon established GxE theory.

Public Health Relevance

This project will provide a comprehensive evaluation of the complex gene-by-environment etiology underlying physical body size on the genome-wide scale. Identification of important gene-by-environment interactions contributing to body mass will reveal important biological mechanisms underlying obesity, detect potential targets for pharmaceutical development and identify populations at risk.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD060726-04
Application #
8469869
Study Section
Special Emphasis Panel (ZRG1-PSE-C (02))
Program Officer
King, Rosalind B
Project Start
2010-09-24
Project End
2015-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$466,734
Indirect Cost
$95,639
Name
University of Colorado at Boulder
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
McQueen, Matthew B; Boardman, Jason D; Domingue, Benjamin W et al. (2015) The National Longitudinal Study of Adolescent to Adult Health (Add Health) sibling pairs genome-wide data. Behav Genet 45:23-Dec
Boardman, Jason D; Domingue, Benjamin W; Daw, Jonathan (2015) What can genes tell us about the relationship between education and health? Soc Sci Med 127:171-80
Boardman, Jason D; Menard, Scott; Roettger, Michael E et al. (2014) Genes in the dopaminergic system and delinquent behaviors across the life course: the role of social controls and risks. Crim Justice Behav 41:713-731
Simonson, Matthew A; McQueen, Matthew B; Keller, Matthew C (2014) Whole-genome pathway analysis on 132,497 individuals identifies novel gene-sets associated with body mass index. PLoS One 9:e78546
Boardman, Jason D; Domingue, Benjamin W; Blalock, Casey L et al. (2014) Is the gene-environment interaction paradigm relevant to genome-wide studies? The case of education and body mass index. Demography 51:119-39
Mollborn, Stefanie; Domingue, Benjamin W; Boardman, Jason D (2014) Understanding multiple levels of norms about teen pregnancy and their relationships to teens' sexual behaviors. Adv Life Course Res 20:1-15
Conley, Dalton; Siegal, Mark L; Domingue, Benjamin W et al. (2014) Testing the key assumption of heritability estimates based on genome-wide genetic relatedness. J Hum Genet 59:342-5
Domingue, Benjamin W; Belsky, Daniel W; Harris, Kathleen Mullan et al. (2014) Polygenic risk predicts obesity in both white and black young adults. PLoS One 9:e101596
Daw, Jonathan (2014) Of kin and kidneys: do kinship networks contribute to racial disparities in living donor kidney transplantation? Soc Sci Med 104:42-7
Haberstick, Brett C; Lessem, Jeffrey M; Hewitt, John K et al. (2014) MAOA genotype, childhood maltreatment, and their interaction in the etiology of adult antisocial behaviors. Biol Psychiatry 75:25-30

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