Genetically Informed Studies of Social Connectedness and Health

7.项目摘要 大量的证据表明，高质量的社会关系与降低风险有关。 一系列疾病结果导致的发病率和死亡率，以及社会脱节和关系不佳 健康质量与健康负面结果的相当大的风险相关。虽然这方面的大部分工作 面积在本质上是相关的，它经常被解释为如果它是因果关系。遗传信息研究方法 可以让研究人员排除流行病学关联的因果解释和/或确定影响 这可能与因果关系相一致。采用双控方法和综合新资料 收集在华盛顿国家双胞胎登记处（WSTR），这项赠款汇集了多样化和建立 一个科学小组研究了一系列关于社会关系、健康和认知能力的悬而未决的问题。 所有这些都集中在因果推理上。本建议中的工作以三个具体目标为指导 （1）对WSTR中的社会关系功能进行详细评估， 这些变量在健康和健康行为的双胞胎分析。我们将进行新的数据收集 对WSTR中的1，000对成年双胞胎（N = 2，000）进行分析，并完成关键关系的“深度表型分析” 质量变量，包括社会融合，关系满意度/质量，和依恋风格。下 目的1，我们还将收集DNA甲基化数据，并使用一系列表观遗传时钟来表征 加速生物老化是我们的主要研究成果之一;（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 双胞胎模特社交孤立和孤独可能会加速认知功能的下降，但这些是 关联符合因果效应吗我们将对患者进行详细的神经心理学评估。 2,000名WSTR参与者使用针对认知结果的评估，显示与 加速的认知衰退、轻度认知障碍和阿尔茨海默病及相关疾病的生物标志物 痴呆症;（3）检查日常社会功能的客观指标与 WSTR中的健康和认知结果。电子激活记录器（Electronically Activated Recorder，缩写为EAE） 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 评估自我报告之外的社会行为。我们将从140名成年人的子样本中收集数据 根据WSTR确定婚姻状况不一致的MZ双胞胎对（N = 280）是否在双胞胎对差异内 社会融合的客观指标与健康、健康行为和认知能力有关 成果。成功完成拟议的研究将有助于建立公共卫生的因果基础 围绕社会关系开展工作。

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.