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: 7989080
• 负责人: NANCY L PEDERSEN
• 金额: $ 70万
• 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 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7989080
• 关键词: Activities of Daily Living; Address; Adoption; Adult; Affect; Age; Age Factors; Aging; American; Area; Arts; Biological; Biological Assay; Biological Markers; Biological Markers; Biometry; Candidate Disease Gene; Categories; Cognitive; Collaborations; Country; Cross-Sectional Studies; Data; Data Analyses; Data Set; Denmark; Development; Elderly; Emotional; Environment; Environmental Risk Factor; Epidemiology; Family Study; Family member; Foundations; Future; Gender; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genotype; Health; Individual; Individual Differences; Intake; Interleukin-6; Investigation; Lead; Life; Life Experience; Living Arrangement; Loneliness; Longitudinal Studies; Low Birth Weight Infant; Measurement; Measures; Mediating; Mental Depression; Meta-Analysis; Methods; Minnesota; Modeling; Nature; Outcome; Outcome Measure; Participant; Personal Satisfaction; Phenotype; Physical Function; Process; Psychometrics; Psychosocial Stress; Registries; Research; Research Personnel; Sampling; Serotonin; Social Environment; Social isolation; Sweden; System; Testing; Twin Multiple Birth; Twin Studies; Well in self; age related; base; cognitive function; design; disability; early childhood; follow-up; gene environment interaction; gene function; inflammatory marker; member; middle age; mortality; offspring; physical conditioning; public health relevance; response; social; theories; tool; young adult

DESCRIPTION (provided by applicant): In this application, we propose a new collaboration among 7 existing longitudinal twin and family studies in Sweden, Denmark, and the US to lay the foundation for future studies of gene-environment interplay through harmonization of these data sets. The central focus is social data that can be related to outcomes in midlife and old age. The studies have a variety of measures relevant to 3 outcome domains: physical functioning and health, psychological well-being (emotional stability/depression), and cognitive health. The studies share a number of indicators of social environment from early childhood through adulthood (e.g. social context, early life experiences, SES). In all, we have data from 7105 twin pairs, age 24 to >90 at baseline, and up to 26 years of longitudinal follow-up. We propose to exploit the as yet unharnessed potential of these studies for considering questions about interplay between social context and late-life outcomes. The first steps will be to harmonize variables that measure outcomes and exposures (Yr 1) using tools such as DataSHaPer to identify overlapping item content and response formats, apply state-of- the-art psychometric analysis to establish measurement variance via IRT-factor approaches, and conduct meta analyses and integrated data analysis of pooled data as warranted. Using existing data, we will capitalize on advantages of the twin design for evaluating GXE and GE correlation, considering both genetic and environmental variance and measured genes and environments. After establishing that such relations exist, we will incorporate measures of inflammatory markers and/or genes (e.g. CRP and IL-6) in Swedish, Danish and American samples as a first concrete step to demonstrate added value of collaboration across these genetically informative twin materials (Yrs 3&4). Finally, we will explore other biological markers and/or genotypes) in relevant analyses of GXE and GE correlation (Yrs 4&5). Using harmonized data, longitudinal and cross-sectional analyses will evaluate conceptual models of gene- environment interplay in late-life functioning by testing the following hypotheses: That stable features of functioning: a) primarily reflect enduring influences of genetic factors, but b) are maintained in part through selection processes whereby high-functioning individuals create environments that reinforce their high functioning (GE correlation); that changes in functioning: a) primarily reflect the influences of environmental factors which b) are mediated in part by individual differences in physical, intellectual, and social activity, as shown by co-twin control methods; and that genetic influences on function in one area can be moderated by factors in other areas. This moderation can overwhelm genetic influences (as when physical disability impacts emotional or cognitive functioning by disrupting individuals' ability to control their environments). Alternatively, moderation can be by factors that trigger genetic vulnerabilities that might not otherwise be expressed (as when psychosocial stress triggers expression of genetic vulnerabilities to physical illness). PUBLIC HEALTH RELEVANCE: Previous research has firmly established the association of social factors with late-life health and functioning. Yet this research does not explain the basis for these associations or how social effects interrelate with the biological and genetic factors known to contribute to late-life functioning. We will establish a consortium of seven longitudinal twin studies to explore the basis for the association of social factors and aging outcomes. The resulting analysis of the combined data from over 16,000 participants aims to understand why early life adversity, social factors such as isolation and loneliness are associated with diverse outcomes including mortality, and physical, emotional and cognitive health.

描述（由申请人提供）：在本申请中，我们提议在瑞典、丹麦和美国现有的 7 项纵向双胞胎和家庭研究之间进行新的合作，通过协调这些数据集为未来基因与环境相互作用的研究奠定基础。中心焦点是可能与中年和老年结果相关的社会数据。这些研究有与 3 个结果领域相关的各种衡量标准：身体机能和健康、心理健康（情绪稳定性/抑郁）和认知健康。这些研究共享从幼儿期到成年期的许多社会环境指标（例如社会背景、早期生活经历、社会经济地位）。总之，我们拥有 7105 对双胞胎的数据，基线年龄为 24 岁至 >90 岁，并且进行了长达 26 年的纵向随访。我们建议利用这些研究尚未开发的潜力来考虑有关社会背景和晚年结果之间相互作用的问题。第一步将是使用 DataSHAPer 等工具来协调测量结果和暴露的变量（第一年），以识别重叠的项目内容和响应格式，应用最先进的心理测量分析，通过 IRT 因子方法建立测量方差，并根据需要对汇总数据进行荟萃分析和综合数据分析。使用现有数据，我们将利用孪生设计的优势来评估 GXE 和 GE 相关性，同时考虑遗传和环境差异以及测量的基因和环境。确定这种关系存在后，我们将在瑞典、丹麦和美国样本中纳入炎症标志物和/或基因（例如 CRP 和 IL-6）的测量，作为第一个具体步骤，以证明这些具有遗传信息的双胞胎材料之间的合作的附加价值（3 年级和 4 年级）。最后，我们将在 GXE 和 GE 相关性（第 4 和第 5 年）的相关分析中探索其他生物标记和/或基因型。使用统一的数据，纵向和横断面分析将通过测试以下假设来评估晚年功能中基因-环境相互作用的概念模型：功能的稳定特征：a）主要反映遗传因素的持久影响，但b）是部分通过选择过程来维持，其中高功能个体创造了增强其高功能的环境（GE相关性）；功能的变化：a) 主要反映环境因素的影响，b) 部分由身体、智力和社会活动的个体差异介导，如双生控制方法所示；并且遗传对某一区域功能的影响可以通过其他区域的因素来调节。这种调节可以压倒遗传影响（当身体残疾通过破坏个人控制环境的能力来影响情绪或认知功能时）。或者，可以通过触发可能不会以其他方式表达的遗传脆弱性的因素来进行调节（例如当心理社会压力触发对身体疾病的遗传脆弱性的表达时）。 公共健康相关性：先前的研究已经牢固地确立了社会因素与晚年健康和功能的关联。然而，这项研究并没有解释这些关联的基础，也没有解释社会效应如何与已知有助于晚年功能的生物和遗传因素相互关联。我们将建立一个由七项纵向双胞胎研究组成的联盟，以探索社会因素与老龄化结果之间关联的基础。对超过 16,000 名参与者的综合数据进行分析，旨在了解为什么早年的逆境、孤立和孤独等社会因素与包括死亡率以及身体、情感和认知健康在内的多种结果相关。