Gene-Environment Interplay of Social Contexts and Aging-Related Outcomes

社会背景和衰老相关结果的基因-环境相互作用

基本信息

批准号：
9340821
负责人：
Margaret Gatz
金额：
$ 81.82万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-15 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9340821
关键词：
Accounting Activities of Daily Living Acute Address Age Aging Alzheimer&apos s Disease Australia Behavior Behavior assessment Behavioral Biometry Birth Buffers Cardiovascular Diseases Chronic Chronic Disease Cognitive Cohort Studies Collaborations Comorbidity Country Data Data Set Dementia Denmark Disease Dizygotic Twins Economics Education Elderly Emotional Environment Environmental Risk Factor Finland Foundations Funding Genes Genetic Genetic Predisposition to Disease Genetic Risk Genetic Variation Genetic study Genotype Goals Health Health Resources Healthy People 2020 High Prevalence Impaired cognition Impairment Income Individual Inequality Intake Life Life Style Literature Longevity Major Depressive Disorder Mediating Medical Methods Modeling Monozygotic twins Morbidity - disease rate Multiple Birth Offspring Nature Obesity Outcome Phenotype Physiological Policies Positioning Attribute Process Publishing Reporting Research Resources Risk Risk Factors Role Same-sex Sample Size Sampling Sex Characteristics Smoking Social Environment Social Welfare Socioeconomic Status Source Staging Sweden Talents Testing Time Twin Multiple Birth Twin Studies Woman Work age related base burden of illness cohort design gene environment interaction genome wide association study health care availability health difference health disparity health equity indexing men physical conditioning programs psychologic public health priorities sex sex disparity skills social socioeconomics success tool

项目摘要

DESCRIPTION (provided by applicant): This competing application seeks to extend, for a further 5 years, the consortium on Interplay of Genes and Environment across Multiple Studies. During the first funding cycle, we established a new collaboration among 8 existing longitudinal twin studies in the U.S., Sweden, and Denmark, set the stage for including an additional 7 longitudinal twin studies from the U.S., Finland, and Australia, and laid the foundation for studying gene- environment interplay in middle and older age through harmonization of these data sets. The aim was to understand how social factors across the lifespan are associated with physical (subjective health, chronic medical illness co-morbidity, functional ability), psychologicl and cognitive health outcomes, particularly in later life. Building on our preliminary results, the proposed work for the next funding cycle focuses on health disparities in aging, in particular, disparities related to socioeconomic status and sex. Health disparities, which have been targeted by Healthy People 2020 as a public health priority, present as paradoxes. SES disparities in aging outcomes, rather than being diminished, have actually been amplified even in modern welfare states with relatively low levels of income inequality and high levels of access to health care. Sex disparities are illustrated by men's shorter lifespans typified by a higher prevalence of acute conditions and women's longer lifespans characterized by a greater chronic disease burden, including higher prevalence of dementia. Through use of the twin design, we propose to identify contextual and individual environmental sources of disparities (differences in exposures and behaviors) and identify how these work in combination with genetic influences (differences in vulnerability). For example, what behaviors and exposures mediate SES disparities? Does high SES buffer genetic influences on health outcomes? Is women's higher rate of disorder due to more years to accumulate adverse exposures, differences in amount of exposure, sex differences in physiological vulnerability to the disorder, or differential genetic o physiological vulnerability to specific exposures compared to men? The answers have implications for how to intervene to reduce disease burden. To evaluate these explanations, we will use co-twin control/within pair models, biometric moderation models, biometric sex limitation models, and polygenic risk scores from genotyping completed during the first funding cycle. Across the 15 twin studies, there are nearly 52,000 individual twins. Within this sample are over 6900 identical twin pairs for within pair difference models, and over 12,500 dizygotic twin pairs including nearly 4000 opposite sex pairs, allowing for testing of hypotheses about sex-specific genetic and environmental influences. The consortium thus uniquely has the sample sizes necessary for the proposed research agenda.

描述（由应用程序提供）：该竞争应用程序旨在再延长5年的5年，即在多个研究中建立基因和环境相互作用的联盟。在第一个融资周期中，我们在美国，瑞典和丹麦的8个现有纵向双胞胎研究中建立了新的合作，为在美国，芬兰和澳大利亚的其他7个纵向双胞胎研究中奠定了基础，并为研究基因环境互动的基础奠定了基础，以通过这些数据集的协调来统一中等年龄。目的是了解整个生命周期中的社会因素如何与身体健康（主观健康，慢性医学疾病，功能能力），心理和认知健康成果相关，尤其是在以后的生活中。以我们的初步结果为基础下一个资金周期的拟议工作重点是衰老的健康差异，尤其是与社会经济地位和性别有关的差异。健康差异是2020年健康人作为公共卫生优先事项的目标，以悖论为悖论。 SES在衰老结果中的差异，而不是被减少，即使在收入不平等和高水平获得医疗保健水平的现代福利国家中，实际上也被放大。性别分布是通过男性较短的寿命来说明的，急性疾病的患病率较高，女性的寿命更长，其特征是慢性病伯恩（Burnen）较大，包括痴呆症患病率较高。通过使用双重设计，我们建议确定分布的上下文和个人环境来源（暴露和行为的差异），并确定它们与遗传影响（脆弱性的差异）结合起来。例如，哪些行为和暴露媒体SES分布？高SES缓冲遗传对健康结果的影响会影响吗？与男性相比，与男性相比，女性是否会因积累不良暴露，暴露量的差异，对疾病的身体脆弱性的性别差异，性别差异的差异，与男性相比，对特定暴露的生理脆弱性的差异，对女性的无序率较高吗？答案对如何进行干预以减少疾病伯恩具有影响。为了评估这些解释，我们将在配对模型，生物识别模型，生物识别性限制模型以及在第一个融资周期完成的基因分型中使用Co-Twin控制/多基因风险评分。在整个15个双胞胎研究中，有将近52,000个单独的双胞胎。在该样本中，对成对差异模型的6900多个相同的双胞胎对，超过12,500多个双叶双胞胎对，其中包括近4000对异性对，可以测试有关性别特异性遗传和环境影响的假设。因此，该财团具有唯一的样本量，该样本量是拟议的研究议程所必需的。