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: 8527659
• 负责人: NANCY L PEDERSEN
• 金额: $ 60.51万
• 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 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8527659
• 关键词: Activities of Daily Living; Address; Adoption; Adult; Affect; Age; Age Factors; Aging; American; Area; Biological; Biological Assay; 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; 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; psychologic; 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，我们提出了在瑞典，丹麦和美国的7种现有纵向双胞胎和家庭研究之间进行新的合作，以通过对这些数据集的协调来为未来的基因环境相互作用奠定基础。中心重点是社会数据可能与中年和老年的成果有关。这些研究具有与3个结果领域相关的各种措施：身体机能和健康，心理健康（情绪稳定/抑郁症）和认知健康。研究从幼儿到成年（例如社会环境，早期生活经验，SES）有许多社会环境指标。总的来说，我们拥有7105个双胞胎的数据，年龄在基线时24至> 90，以及长达26年的纵向随访。我们建议利用这些研究的潜力尚未考虑，以考虑有关社会环境和晚期结果之间相互作用的问题。第一步将是使用诸如DataShaper之类的工具来统一变量和曝光（YR 1）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以通过IRT因子方法来建立测量方差，并进行元分析和进行元数据分析，以授予授权。使用现有数据，我们将考虑遗传和环境方差以及测量基因和环境的双重设计的优势来评估GXE和GE相关性。确定存在这种关系后，我们将纳入瑞典语，丹麦和美国样本中的炎症标记和/或基因（例如CRP和IL-6）的度量，作为在这些遗传信息丰富的双胞胎材料（YRS 3＆4）中展示协作附加协作价值的第一步。最后，我们将在GXE和GE相关性的相关分析中探索其他生物标记和/或基因型（YRS 4和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);功能的变化：a）主要反映了b）的环境因素的影响，部分是由人体，智力和社会活动的个体差异所介导的，如Co-Twin Control方法所示；遗传对一个区域功能的影响可以由其他领域的因素进行调节。这种节制会压倒遗传影响（就像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）。另外，节制可能是由于触发遗传脆弱性的因素而言，这些因素可能不会表达出来（例如，当社会心理压力触发遗传脆弱性对身体疾病的表达时）。 公共卫生相关性：以前的研究已经牢固地建立了社会因素与晚期健康和功能的关联。然而，这项研究并不能解释这些关联的基础，也不能解释社会影响与已知有助于晚期功能的生物学和遗传因素相互关联的基础。我们将建立一个七个纵向双胞胎研究的财团，以探索社会因素和老龄化结果的关联基础。对来自16,000多名参与者的合并数据的结果分析旨在了解为什么早期的逆境，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各种结果有关。