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 #
5R01HD060726-03
Application #
8288611
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
2012-06-01
Budget End
2013-05-31
Support Year
3
Fiscal Year
2012
Total Cost
$580,674
Indirect Cost
$127,025
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
Demmitt, Brittany A; Corley, Robin P; Huibregtse, Brooke M et al. (2017) Genetic influences on the human oral microbiome. BMC Genomics 18:659
Roettger, Michael E; Boardman, Jason D; Harris, Kathleen Mullan et al. (2016) The association between the MAOA 2R genotype and delinquency over time among men: the interactive role of parental closeness and parental incarceration. Crim Justice Behav 43:1076-1094
Domingue, Benjamin W; Wedow, Robbee; Conley, Dalton et al. (2016) Genome-Wide Estimates of Heritability for Social Demographic Outcomes. Biodemography Soc Biol 62:1-18
Nowotny, Kathryn M; Peterson, Rachel L; Boardman, Jason D (2015) Gendered contexts: variation in suicidal ideation by female and male youth across U.S. states. J Health Soc Behav 56:114-30
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
Wehby, George L; Domingue, Benjamin W; Boardman, Jason D (2015) Prevention, Use of Health Services, and Genes: Implications of Genetics for Policy Formation. J Policy Anal Manage 34:519-36
Domingue, Benjamin W; Belsky, Daniel; Conley, Dalton et al. (2015) Polygenic Influence on Educational Attainment: New evidence from The National Longitudinal Study of Adolescent to Adult Health. AERA Open 1:1-13
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 45:12-23
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
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

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