SES health gradients in late life: testing models of gene-environment interplay in an international twin consortium

晚年的 SES 健康梯度：在国际双胞胎联盟中测试基因与环境相互作用的模型

基本信息

批准号：
9770742
负责人：
Brian K. Finch
金额：
$ 55.5万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9770742
关键词：
Accounting Activities of Daily Living Address Adult Affect Age Aging Area Australia Blood Pressure Body mass index Capital Characteristics Chronic Disease Classification Cognitive Cohort Studies Collaborations Coronary Arteriosclerosis Country Data Data Collection Data Set Denmark Disease Disease susceptibility Dizygotic Twins Economic Conditions Education Elderly Emotional Environment Environmental Risk Factor Exposure to Financial Hardship Finland Genes Genetic Genetic Predisposition to Disease Genotype Goals Hand Strength Health Health Policy Health Promotion Health Status Healthy People 2020 Human Income Individual Inequality Inherited Intake International Life Cycle Stages Life Style Loneliness Measures Mediating Mental Depression Methods Modeling Monozygotic twins Nature Occupational Occupations Outcome Participant Phenotype Physical Exercise Prevention strategy Quantitative Genetics Research Research Personnel Resources Respiratory physiology Risk Role Sampling Sex Differences Social Class Social Policies Social status Social stratification Societies Socioeconomic Status Stress Structure Sweden Testing Time Toxic effect Translating Twin Multiple Birth Twin Studies Vision Woman Women&apos s Health Work cohort cost effective design disorder risk environmental enrichment for laboratory animals genome-wide health economics indexing innovation low socioeconomic status memory process men physical conditioning population health processing speed public health priorities safety net sex social social health determinants social inequality socioeconomics tool

项目摘要

Inequalities in health outcomes are targeted by Healthy People 2020 as a public health priority. The social stratification of health is well documented, pervasive, and of growing concern because it appears to be increasing over time. Reducing these social class disparities will require greater understanding of how social class impacts health than we currently have. While most research focuses on individual-level socioeconomic status—defined as social status that accrues to occupational classification, education, and income—new research has begun to focus on the macro-economic environment. Further, although both genetic (G) and environmental (E) factors are known to contribute to the SES-health gradient, the mechanisms by which the two sets of factors combine to influence health outcomes (i.e., GE interplay) are poorly understood. Models of GE interplay differ in their environmental focus (disease-triggering effects of toxic environments vs. health- promoting benefits of favorable environments) and the expected genetic contribution to disease (maximized in adverse environments, in favorable environments, or at both extremes) Understanding whether high-SES preferentially promotes good health among a genetically selected subset of individuals (i.e., social enhancement), whether low-SES triggers poor health among a genetically vulnerable subset of individuals (i.e., diathesis-stress), or both, is essential for translating research in this area into effective prevention strategies. The consortium on Interplay of Genes and Environments across Multiple Studies (IGEMS) with 16 existing longitudinal twin studies in the U.S., Sweden, Denmark, Finland, and Australia is poised to evaluate these models. IGEMS includes more than 52,000 individual twins, with over 7000 identical twin pairs for within-pair difference models, and over 12,600 dizygotic twin pairs with nearly 4000 opposite sex pairs for sex-difference models. The sample spans a wide age range (15 to 103 years at intake) and includes a set of well-characterized longitudinal phenotypes, including harmonized measures of physical health (e.g., subjective health, chronic disease indicators, body mass index, lung function, blood pressure, activities of daily living, and grip strength), cognitive health (verbal ability, spatial ability, memory, and processing speed), and emotional health (depression, loneliness) as well as measures of multiple facets of SES (e.g., occupation, education, financial strain). In addition, a large subset of IGEMS participants has genome wide genotyping from which we have computed polygenic risk scores (PRS). We will use co-twin control/within pair models, quantitative genetic moderation, sex-limitation models, and PRS analyses to investigate specific mechanisms of the SES-health gradient at the individual level as well as the country and historical cohort level (e.g., country-level indices of social inequality). The proposed study reflects an innovative vision by the investigators who—rather than addressing the research questions through new data collection—successfully created a collaboration among 16 large international studies with relevant phenotypes, making this study highly cost-effective and efficient.

健康成果的不平等是2020年健康人的目标。社交健康分层是有充分的文献记载，普遍性和日益关注的，因为它似乎是随着时间的推移增加。减少这些社会阶层差异将需要对社会的社会方式有更多了解班级影响健康比我们目前的健康。虽然大多数研究都集中于个人级别的社会经济地位 - 定义为累积职业分类，教育和收入的社会地位 - 研究已开始关注宏观经济环境。此外，尽管遗传（G）和已知环境（E）因素有助于SES健康梯度，该机制的机制两组因素结合起来影响健康结果（即GE相互作用）的理解很少。模型 GE相互作用不同的环境重点（有毒环境的触发效应与健康的影响促进有利环境的益处）和对疾病的预期遗传贡献（最大化不利的环境，有利的环境或两个极端）优先在一个普遍选择的个体子集中促进身体健康（即社会增强），低SES是否会触发一个普遍脆弱的个体子集中的健康状况不佳（即透明的压力）或两者兼有两者，对于将该领域的研究转化为有效的预防策略至关重要。多项研究（IGEM）与16个现有的基因和环境相互作用的联盟在美国，瑞典，丹麦，芬兰和澳大利亚的纵向双胞胎研究被毒死以评估这些型号。 IGEM包括超过52,000个单独的双胞胎，配对内有7000多个双胞胎对差异模型，超过12,600多个双卵双胞胎对，近4000个相反对的性别差异型号。样品跨越了年龄范围（入学时15至103年），其中包括一组良好的特征纵向表型，包括对身体健康的统一测量（例如，主观健康，慢性疾病指标，体重指数，肺功能，血压，日常生活活动和抓地力），认知健康（言语能力，空间能力，记忆和处理速度）和情绪健康（抑郁，孤独）以及SES多个方面的度量（例如职业，教育，财务拉紧）。此外，大量的IGEM参与者具有广泛的基因组基因分型，我们从中拥有该基因组计算的多基因风险评分（PRS）。我们将在配对模型中使用Co-Twin控件/定量通用适度，性限制模型和PRS分析，以研究SES健康的特定机制在个人层面以及国家和历史队列层面上的梯度（例如，国家一级指数社会不平等）。拟议的研究反映了调查人员的创新愿景通过新的数据收集来解决研究问题 - 成功地建立了合作 16个具有相关表型的大型国际研究，这使得这项研究具有高度成本效益和有效的效率。