Social Demographic Moderation of Genome Wide Associations for Body Mass Index

描述（由申请人提供）：来自生物计量学和分子研究的证据表明，遗传因素显著影响人类的体重。这导致了最近在整个人类基因组中识别与成人和青少年体重相关的单核苷酸多态性（snp）的努力。然而，所有现有的关于体重和肥胖的全基因组关联（GWA）研究都侧重于主要的遗传效应，而不是遗传和环境因素之间的相互作用。这导致了基因-环境相互作用（GxE）研究的重点是调节遗传主效应的环境因素。如果在特定环境中只有遗传效应（例如，没有主要的遗传效应），那么目前的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，由于体重的遗传关联取决于社会环境影响，因此必须将环境风险（和保护）因素包括在对全球环境影响的概念理解和方法方法中。虽然涉及单一遗传变异的GxE研究越来越普遍，但没有现有的工作专门关注GxE的全基因组方法。我们的方法是一种全新的方法来研究遗传对体重的影响，扩展了已有的GWA方法，并借鉴了已有的GxE理论。

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.