Genetically Informed Studies of Social Connectedness and Health

社会联系与健康的遗传学研究

• 批准号: 10503656
• 负责人: DAVID A SBARRA
• 金额: $ 91.83万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10503656
• 关键词: Address; Adult; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Area; Behavioral Genetics; Biological Aging; Cell Aging; Cognitive; DNA Methylation; Data; Data Collection; Data Set; Dementia; Disease Outcome; Elderly; Epidemiology; Epigenetic Process; Foundations; Grant; Health; Health behavior; Human; Impaired cognition; Individual; Learning; Literature; Loneliness; Marital Status; Marriage; Measures; Memory; Methods; Methylation; Modeling; Monozygotic twins; Morbidity - disease rate; Nature; Neuropsychology; Outcome; Outcome Study; Participant; Pathway interactions; Patient Self-Report; Persons; Phenotype; Records; Registries; Research; Research Design; Research Methodology; Research Personnel; Risk; Sampling; Series; Social Behavior; Social Functioning; Social isolation; Social support; Testing; Time; Twin Multiple Birth; Twin Studies; Variant; Washington; Well in self; Woman; Work; base; cognitive function; cohort; design; epidemiologic data; epigenome-wide association studies; experience; field study; gender difference; indexing; men; middle age; mild cognitive impairment; mood symptom; mortality; neuroimaging; pandemic coronavirus; public health intervention; satisfaction; smartphone Application; social; social integration; social relationships; sound

7. PROJECT SUMMARY A large body of evidence indicates that high-quality social relationships are correlated with decreased risk for morbidity and mortality from a range of disease outcomes, and that social disconnection and poor relationship quality are correlated with considerable risk for negative health outcomes. Although most of the work in this area is correlational in nature, it is often interpreted as if it is causal. Genetically informed research methods can allow researchers to rule-out causal explanations for epidemiological associations and/or identify effects that may be consistent with a causal influence. Using co-twin control methods and a comprehensive new data collection in the Washington State Twin Registry (WSTR), this grant brings together a diverse and established scientific team to examine a series of unanswered questions around social relationships, health, and cognitive functioning, all of which center on causal inference. The work in this proposal is guided by three Specific Aims that will: (1) Conduct a detailed assessment of social relationship functioning in the WSTR and use these variables in co-twin analyses of health and health behaviors. We will conduct a new data collection on 1,000 adult twin pairs (N = 2,000) in the WSTR and complete a “deep phenotyping” of key relationship quality variables, including social integration, relationship satisfaction/quality, and attachment styles. Under Aim 1, we will also collect DNA methylation data and use a series of epigenetic clocks to characterize accelerated biological aging among our main study outcomes; (2) Conduct a detailed neuropsychological assessment of cognitive functioning in the WSTR cohort and use these variables as key outcomes in co-twin models. Social isolation and loneliness may hasten declines in cognitive functioning, but are these associations consistent with a causal effect? We will conduct detailed neuropsychological assessments of the 2,000 WSTR participants using assessments that target cognitive outcomes shown to be associated with accelerated cognitive decline, mild cognitive impairment, and biomarkers of Alzheimer’s disease and related dementias; and (3) Examine the association between objective measures of daily social functioning and the health and cognitive outcomes in the WSTR. The Electronically Activated Recorder (EAR) is a smartphone application that records ambient sounds in participants’ daily lives and provides a means of assessing social behaviors beyond self-report alone. We will collect EAR data from a sub-sample of 140 adult MZ twin pairs discordant for marital status (N = 280) from the WSTR to determine if within twin-pair differences in the objective indices of social integration are associated with the health, health behavior, and cognitive outcomes. Successful completion of the proposed research will help build a causal foundation for public health intervention efforts around social relationships.

7.项目总结 大量证据表明，高质量的社会关系与降低患病风险相关。 一系列疾病后果的发病率和死亡率，以及社会脱节和不良关系 质量与负面健康结果的相当大风险相关。尽管这方面的大部分工作 面积在本质上是相关的，它经常被解释为似乎是因果的。遗传信息研究方法 可以允许研究人员排除流行病学关联的因果解释和/或确定影响 这可能与因果影响是一致的。采用同孪生控制方法和全面的新数据 华盛顿州双胞胎登记处(WSTR)的收藏，这笔赠款汇集了一个多样化和成熟的 研究围绕社会关系、健康和认知的一系列悬而未决的问题的科学团队 功能，所有这些都以因果推理为中心。这项提案中的工作以三个具体目标为指导 这将：(1)对WSTR中社会关系的运作和使用进行详细评估 这些变量在健康和健康行为的双胞胎分析中。我们将进行一次新的数据收集 对WSTR中的1,000对成年双胞胎(N=2,000)进行研究，并完成关键关系的“深层表型” 质量变量，包括社会融合、关系满意度/质量和依恋风格。在……下面 目标1，我们还将收集DNA甲基化数据，并使用一系列表观遗传学时钟来表征 加速生物衰老是我们的主要研究成果；(2)进行详细的神经心理学研究 评估WSTR队列中的认知功能，并将这些变量用作 同卵双胞胎。社交孤立和孤独可能会加速认知功能的下降，但这些是 与因果结果相一致的关联？我们将对患者进行详细的神经心理评估 2,000名WSTR参与者使用针对认知结果的评估，结果显示与 认知功能减退加速、轻度认知损害与阿尔茨海默病及相关的生物标记物 以及(3)研究日常社会功能的客观衡量标准与 WSTR中的健康和认知结果。电子激活记录器(EAR)是一种 智能手机应用程序，记录参与者日常生活中的环境声音，并提供一种方式 评估社会行为，而不仅仅是自我报告。我们将从140名成年人的样本中收集耳朵数据 来自WSTR的MZ双胞胎对婚姻状况不一致(N=280)，以确定双胞胎对之间的差异 在社会融合的客观指标中，与健康、健康行为和认知相关 结果。成功完成拟议的研究将有助于为公共卫生奠定因果基础 围绕社会关系的干预努力。