Project 4 -- MIDUS Genomics Project

摘要-基因组学项目 MIDUS基因组学项目提供基因组数据资源、分析工具和方法培训， 推进MIDUS的总体目标，即确定心理社会因素与健康之间的关系， 与衰老有关的结果。该项目提供的资源包括：1）基于双胞胎的研究策略， 确定对心理社会和健康结果的总体遗传影响; 2）全基因组RNA谱， 确定介导这些影响的特定基因表达途径; 3）全基因组DNA 甲基化谱，以确定介导这些影响的特定表观遗传途径; 4）全基因组 单核苷酸多态性谱，以确定特定的遗传多态性和多基因 风险概况; 5）对与MIDUS研究特别相关的特定基因变体进行靶向基因分型 目标，如与阿尔茨海默病相关的APOE基因;以及6）MIDUS培训 研究人员在基因组数据的特殊实质性和分析方面。基因组测量是 从MIDUS生物标志物项目（核心MIDUS和MIDUS）的大约1200名参与者中收集 刷新样品），并包括2波RNA和DNA甲基化谱，可以量化的速率， 生物老化以及炎症生物学和抗病毒生物学随时间的变化。MIDUS的目标 基因组学项目包括：目的1：收集和传播RNA基因表达谱，DNA甲基化 目标2：分析心理社会风险过程之间的关系 (e.g.,社会经济和社会关系不利因素）和复原力进程（例如，心理健康- 存在和社会资源），和纵向变化率的“保守转录反应， “表观遗传年龄”和死亡风险的“逆境”（CTRA）RNA谱和DNA甲基化测量;目标3： 定义CTRA基因表达和表观遗传年龄加速之间的关系，以确定其 与健康、福祉和疾病风险的相关性和各自的关系。基因组数据由 该项目提供了MIDUS整体综合生物心理社会的基本遗传和分子要素 对中年美国人健康和幸福的描述。

ABSTRACT – GENOMICS PROJECT The MIDUS Genomics Project provides genomic data resources, analytic tools, and methodological training to advance the overall MIDUS objective of defining the relationship between psychosocial factors and health- and aging-related outcomes. Resources provided by this project include: 1) twin-based research strategies to identify overall genetic influences on psychosocial and health outcomes; 2) genome-wide RNA profiles to identify the specific gene expression pathways that mediate these influences; 3) genome-wide DNA methylation profiles to identify the specific epigenetic pathways that mediate these influences; 4) genome-wide single-nucleotide polymorphism profiles to identify the role of specific genetic polymorphisms and polygenic risk profiles; 5) targeted genotyping of specific gene variants of particular relevance to MIDUS research objectives, such as the APOE gene associated with Alzheimer’s Disease; and 6) training to MIDUS investigators in the special substantive and analytic aspects of genomic data. Genomic measures are collected from approximately 1200 participants in the MIDUS Biomarker Project (Core MIDUS and MIDUS Refresher samples), and include 2 waves of RNA and DNA methylation profiles that can quantify rates of biological aging and change over time in inflammatory biology and antiviral biology. Aims of the MIDUS Genomics Project include: Aim 1: Collect and disseminate RNA gene expression profiles, DNA methylation profiles, and targeted genotyping data; Aim 2: Analyze the relationship between psychosocial risk processes (e.g., socio-economic and socio-relational disadvantage) and resilience processes (e.g., psychological well- being and social resources), and longitudinal rates of change in the “Conserved Transcriptional Response to Adversity” (CTRA) RNA profile and DNA methylation measures of “epigenetic age” and mortality risk; Aim 3: Define the relationship between CTRA gene expression and epigenetic age acceleration to determine their correlation and respective relationships to health, well-being, and disease risk. The genomic data provided by this project provide essential genetic and molecular elements of MIDUS’s overall integrative biopsychosocial characterization of health and well-being of mid-life Americans.