Identifying gene-by-environment interplay in health behavior

识别健康行为中基因与环境的相互作用

• 批准号: 10253129
• 负责人: Titus Johannes Galama
• 金额: $ 84.19万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10253129
• 关键词: Address; Adolescence; Adolescent; Adult; Affect; Age; Aging; Alcohol consumption; American; Caring; Cessation of life; Characteristics; Child; Childhood; Cigarette; Collection; Data; Data Set; Diet; Dimensions; Disability Insurance; Disease; Economics; Endowment; Environment; Environmental Exposure; Etiology; Evaluation; Evolution; Exhibits; Framingham Heart Study; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genotype; Health; Health Professional; Health and Retirement Study; Health behavior; Health behavior outcomes; Individual; Intervention; Investigation; Knowledge; Labor Forces; Life; Life Cycle Stages; Long-Term Effects; Longevity; Longitudinal Studies; Measures; Medical; Methods; Modeling; Natural experiment; Nature; Obesity; Occupations; Parents; Pathway interactions; Pattern; Phase; Phenotype; Play; Policies; Population Group; Research; Research Personnel; Role; Sample Size; Schools; Shapes; Smoke; Smoking; Social Policies; Socioeconomic Status; Source; Structural Models; Structure; Taxation; Testing; Tobacco use; Variant; Withdrawal; base; biobank; experimental study; genetic analysis; genetic variant; genome wide association study; health disparity; high risk; improved; innovation; insight; intervention effect; low socioeconomic status; mortality; non-smoker; novel; physical inactivity; socioeconomics; theories; therapy design; unemployment insurance

Project summary / abstract Smoking, alcohol consumption, and obesity are the three leading causes of preventable disease and death in the U.S. Each year tobacco use alone kills nearly 440,000 Americans, who die up to 15 years earlier than nonsmokers. Risky health behaviors are more prevalent among low socioeconomic status (SES) groups, and significant sources of the substantial disparities in health between them. Such disparities are formed early in life and become more pronounced as individuals age. In this application we seek to test the hypothesis that protective socioeconomic and policy environments moderate the effects of high-risk genetic variants for smoking, alcohol consumption, and obesity; evaluate how such gene-by-environment (GxE) interplay evolves over the lifecycle and how it contributes to health disparities; generate information relevant to decision makers and health professionals; and when possible investigate the underlying mechanisms. Using results from genome-wide association studies (GWAS), we focus on specific genetic variants or aggregated genetic scores and specific dimensions of the socioeconomic and policy environment. The proposed research is a natural continuation of our project, “From understanding to reducing health disparities: a model-based evaluation” (R01 AG037398), in which we developed a theory of the formation and evolution of health disparities between SES groups, and informed by the theory, explored the extent to which disparities in health and longevity between SES groups are the result of differences in job-conditions, health behavior, medical care, and labor-force withdrawal. We also investigated the effects of possible policy interventions on health and health disparities. Two key findings of that research are that: (i) health behaviors play a very important role in health disparities between SES groups, and (ii) multiple factors (that have a genetic basis) influence both SES and health, and interact with SES in producing health. This suggests an important role for interactions between genes and the environment in shaping health behavior. With the very recent order of magnitude increases in the power of polygenic prediction, and the very recent genetic discovery results for several new smoking, alcohol consumption, and obesity phenotypes, it is now possible to incorporate into our analyses the effects of genetic predispositions, in interaction with the socioeconomic and policy environment, on these three risky health behaviors. The proposed project will integrate several complementary methods: descriptive analyses to explore associations for different levels of genetic risk and different measures of the social and policy environment at different stages of life; estimation of structural lifecycle models to better understand GxE interplay and make predictions; exploitation of natural experiments to address causality; and counterfactual analyses, using the structural models, to evaluate intervention alternatives.

项目概要/摘要 吸烟、饮酒和肥胖是美国可预防疾病和死亡的三大主要原因。 美国每年仅烟草使用就导致近44万美国人死亡，他们比美国人早15年死亡。 不吸烟的人。危险的健康行为在低社会经济地位（SES）群体中更为普遍， 这是造成他们之间健康差距的重要原因。这种差异在早期就形成了。 随着年龄的增长，它变得更加明显。 在这个应用程序中，我们试图测试的假设，保护社会经济和政策环境， 缓和高风险遗传变异对吸烟、饮酒和肥胖的影响;评估如何 这种基因与环境（GxE）的相互作用在整个生命周期中不断演变，以及它如何对健康做出贡献 差异;产生与决策者和卫生专业人员相关的信息;以及在可能的情况下 研究潜在的机制。利用全基因组关联研究（GWAS）的结果，我们 重点关注特定的遗传变异或汇总的遗传分数和社会经济的特定方面， 和政策环境。 拟议的研究是我们项目的自然延续，“从了解到减少健康 差异：基于模型的评估”（R 01 AG 037398），其中我们开发了一种形成理论， 社会经济地位群体之间的健康差距的演变，并通过理论，探讨了在何种程度上， 社会经济地位群体之间在健康和寿命方面的差异是工作条件、健康状况、 行为、医疗保健和劳动力退出。我们还调查了可能的政策的影响， 健康和健康差距的干预措施。该研究的两个主要发现是：（一）健康行为 在SES群体之间的健康差异中发挥着非常重要的作用，以及（ii）多种因素（具有 遗传基础）影响社会经济地位和健康，并与社会经济地位相互作用，产生健康。这表明有 基因和环境之间的相互作用在塑造健康行为中的重要作用。与非常 多基因预测能力的最近数量级增加，以及最近的基因发现， 结果对于一些新的吸烟，饮酒和肥胖表型，现在有可能 在我们的分析中纳入遗传倾向的影响，与社会经济和 政策环境，对这三个危险的健康行为。 拟议的项目将整合几种互补的方法：描述性分析，以探讨 不同程度的遗传风险和不同的社会和政策环境的措施， 生命的不同阶段;评估结构生命周期模型，以更好地了解GxE相互作用， 预测;利用自然实验来解决因果关系;以及反事实分析，使用 结构模型，以评估干预方案。