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

 描述（由申请人提供）：该竞争性申请旨在将多项研究中基因与环境相互作用的联盟再延长5年。在第一个资助周期中，我们在美国现有的8项纵向双胞胎研究中建立了新的合作，瑞典和丹麦为纳入另外7项来自美国的纵向双胞胎研究奠定了基础，芬兰和澳大利亚，并通过协调这些数据集，为研究中老年基因-环境相互作用奠定了基础。目的是了解整个生命周期的社会因素如何与身体（主观健康，慢性医学疾病合并症，功能能力），心理和认知健康结果相关，特别是在晚年。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化中的健康差距，特别是与社会经济地位和性别有关的差距。《2020年健康人》将健康差距作为公共卫生优先事项，但这些差距却表现为悖论。即使在收入不平等程度相对较低、医疗保健水平较高的现代福利国家，社会经济地位在老龄化结果方面的差距非但没有缩小，反而被放大了。男性的寿命较短，其典型特征是急性疾病的发病率较高，而女性的寿命较长，其特点是慢性疾病负担较大，包括痴呆症的发病率较高。通过使用双胞胎设计，我们建议识别差异的背景和个人环境来源（暴露和行为的差异），并确定这些工作如何与遗传影响（脆弱性的差异）相结合。例如，什么样的行为和暴露介导了SES差异？高社会经济地位是否缓冲了遗传对健康结果的影响？女性患病率较高是由于累积不良暴露的年数较多、暴露量的差异、对疾病的生理脆弱性的性别差异，还是与男性相比，对特定暴露的遗传或生理脆弱性差异？这些答案对如何干预以减少疾病负担具有启示意义。为了评估这些解释，我们将使用双胞胎控制/配对内模型，生物计量适度模型，生物计量性别限制模型，以及在第一个资助周期完成的基因分型的多基因风险评分。在15项双胞胎研究中，有近52，000对双胞胎。在这个样本中有超过6900对同卵双胞胎对内差异模型，和超过12,500双卵双胞胎对，包括近4000对异性对，允许测试的假设性别特异性遗传和环境的影响。因此，该联盟独特地拥有拟议研究议程所需的样本量。

 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.