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.

项目摘要 /摘要 吸烟，饮酒和肥胖是可预防疾病和死亡的三个主要原因 美国每年仅使用烟草就会杀死近44万美国人，他们死于15年 非吸烟者。在低社会经济地位（SES）群体中，风险的健康行为更为普遍，并且 它们之间健康分布的重要来源。这样的分布是在早期形成的 随着个人的年龄，生活和变得更加明显。 在此应用程序中，我们试图检验保护社会经济和政策环境的假设 调节高风险遗传变异对吸烟，饮酒和肥胖的影响；评估如何 这种基因环境（GXE）相互作用的演变及其对健康的贡献 分布；生成与决策者和卫生专业人员有关的信息；并在可能的情况下 研究潜在机制。使用全基因组关联研究（GWAS）的结果，我们 专注于特定的遗传变异或汇总遗传评分以及社会经济的特定维度 和政策环境。 拟议的研究是我们项目的自然延续，“从理解到降低健康 差异：基于模型的评估”（R01 AG037398），在其中我们开发了形成理论和 SES群体之间健康差异的演变，并由理论告知，探讨了多大程度上的程度 SES组之间的健康和寿命差异是工作条件差异，健康的结果 行为，医疗保健和劳动力提取。我们还调查了可能的政策的影响 健康和健康差异的干预措施。该研究的两个关键发现是：（i）健康行为 在SES组之间的健康差异中起着非常重要的作用，以及（ii）多个因素（具有 遗传基础）影响SES和健康，并与SES相互作用在产生健康方面。这表明一个 基因与环境之间相互作用的重要作用在塑造健康行为中。与 多基因预测的力量和最近的遗传发现的最新数量级增加了 几种新的吸烟，饮酒和肥胖表型的结果，现在可以 将我们的分析纳入遗传易感性的影响，与社会经济和社会经济相互作用 政策环境，这三种危险的健康行为。 拟议的项目将集成几种完整的方法：描述性分析以探索 在不同水平的遗传风险和社会和政策环境的不同措施的关联 生活的不同阶段；估计结构生命周期模型，以更好地理解GXE相互作用并使 预测；对自然实验的开采以解决休闲；和反事实分析，使用 结构模型，以评估干预措施。