Social Demographic Moderation of Genome Wide Associations for Body Mass Index

描述(由申请人提供)：来自生物测定和分子研究的证据表明，遗传因素显著影响人类的体重。这导致了最近的努力，以确定与成人和青少年体重相关的整个人类基因组的单核苷酸多态(SNPs)。然而，现有的所有关于体重和肥胖的基因组范围关联(GWA)研究都集中在主要的遗传效应上，而不是遗传和环境因素之间的交互作用。这导致了基因-环境相互作用(GxE)研究的重点是适度遗传主效应的环境因素。如果在特定环境中只存在遗传效应(例如，没有主遗传效应)，那么当前的GWA模型将忽略重要的遗传影响。由于体重受到社会环境因素的强烈影响，以及体重的遗传关联取决于社会环境影响，环境风险(和保护性)因素必须包括在对GWA的概念理解和方法方法中。虽然涉及单一遗传变异的GxE研究越来越常见，但现有的工作还没有专门关注GxE的全基因组方法。我们的方法是一种检查遗传对体重影响的全新方法，它扩展了已建立的GWA方法并借鉴了已建立的GxE理论。 公共卫生相关性：该项目将在全基因组范围内对身体大小背后复杂的基因和环境病因学进行全面评估。识别导致体重的重要基因-环境相互作用将揭示导致肥胖的重要生物学机制，发现潜在的药物开发靶点，并确定“处于危险”的人群。

DESCRIPTION (provided by applicant): 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".