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

• 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
• 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' 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

 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（由申请人提供）：本竞争性申请旨在将基因与环境相互作用跨多项研究的联盟再延长 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，为纳入来自美国、芬兰和澳大利亚的另外 7 项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、慢性疾病共病、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方面的健康差异，特别是与社会经济地位和性别有关的差异。 《2020 年健康人民》将健康差异作为公共卫生优先事项，但它却以悖论的形式出现。即使在收入不平等程度相对较低且获得医疗保健的机会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异非但没有缩小，反而进一步扩大。男性寿命较短，其特点是急性疾病患病率较高，而女性寿命较长，其特点是慢性疾病负担较大，包括痴呆症患病率较高，这说明了性别差异。通过使用孪生设计，我们建议确定差异的背景和个体环境来源（暴露和行为的差异），并确定这些差异如何与遗传影响（脆弱性的差异）结合起来。例如，哪些行为和接触会调节社会经济地位差异？高社会经济地位是否可以缓冲遗传对健康结果的影响？与男性相比，女性患病率较高是否是由于积累不良暴露的年数更长、暴露量的差异、对疾病的生理脆弱性的性别差异，或者对特定暴露的遗传或生理脆弱性不同？这些答案对于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，我们将使用双胞胎控制/配对模型、生物识别调节模型、生物识别性别限制模型以及第一个资助周期内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 名双胞胎。该样本中有超过 6900 对同卵双胞胎用于配对差异模型，以及超过 12,500 对异卵双胞胎，其中包括近 4000 对异性对，从而可以检验有关性别特异性遗传和环境影响的假设。因此，该联盟拥有独特的拟议研究议程所需的样本量。