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

 描述(由申请人提供)：这项竞争申请旨在将跨多个研究的基因与环境相互作用联盟再延长5年。在第一个资助周期中，我们在美国、瑞典和丹麦现有的8项纵向双胞胎研究之间建立了新的合作关系，为纳入另外7项来自美国、芬兰和澳大利亚的纵向双胞胎研究奠定了基础，并通过协调这些数据集为研究中老年基因与环境的相互作用奠定了基础。其目的是了解整个生命周期中的社会因素如何与身体(主观健康、慢性疾病并存、功能能力)、心理和认知健康结果相关，特别是在以后的生活中。根据我们的初步结果， 下一个供资周期的拟议工作重点是老龄方面的健康差距，特别是与社会经济地位和性别有关的差距。健康人2020年将健康差距列为公共卫生优先事项，这是一种悖论。即使在收入不平等程度相对较低、获得医疗保健水平较高的现代福利国家，社会保障部门在老龄化结果方面的差距不仅没有缩小，实际上也被放大了。性别差异表现为男性寿命较短，表现为急性疾病的发病率较高，而女性寿命较长，其特点是慢性病负担较重，包括痴呆症患病率较高。通过使用双胞胎设计，我们建议确定背景和个人环境差异的来源(暴露和行为的差异)，并确定这些因素如何与遗传影响(脆弱性差异)相结合。例如，哪些行为和暴露会调节SES差异？高SES是否缓冲了基因对健康结果的影响？与男性相比，女性患病率较高的原因是累积不良暴露的年限较长、暴露的数量不同、生理易感性方面的性别差异，还是对特定暴露的不同遗传或生理易感性？这些答案对如何进行干预以减轻疾病负担具有重要意义。为了评估这些解释，我们将使用共同双胞胎对照/内配对模型、生物计量调节模型、生物计量性别限制模型以及在第一个资金周期内完成的基因分型的多基因风险分数。在15项双胞胎研究中，有近5.2万对单独的双胞胎。在这个样本中，有超过6900对同卵双胞胎用于内差模型，超过12,500对异卵双胞胎包括近4000对异性对，允许测试关于性别特定遗传和环境影响的假设。因此，该联盟独一无二地拥有拟议研究议程所需的样本数量。

 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.