Relationships among Genetic Regulators of Aging Health and Lifespan

衰老健康与寿命的基因调节因子之间的关系

基本信息

批准号：
8668227
负责人：
ANATOLIY I YASHIN
金额：
$ 175.2万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-15 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8668227
关键词：
21 year old Address Adverse effects Age Aging Aging-Related Process Area Biological Biological Process Cardiovascular Diseases Complex Data Data Set Diabetes Mellitus Discipline Disease Elderly Environment Epistatic Gene Future Genes Genetic Genetic Predisposition to Disease Health Human Human body Individual Knowledge Life Life Cycle Stages Link Literature Longevity Malignant Neoplasms Methodology Methods Modeling Molecular National Institute on Aging Nature Organism Outcome Pathway interactions Phenotype Physiological Preventive Intervention Principal Investigator Process Public Health Regulation Research Risk Role SNP genotyping Shapes Statistical Models Stochastic Processes Systems Biology age group base computerized data processing data management disability gene environment interaction genetic analysis genetic profiling genetic variant genome wide association study genome-wide healthy aging human disease improved indexing medical complication mortality next generation sequencing non-genetic preempt prevent programs public health relevance routine care trait

项目摘要

DESCRIPTION (provided by applicant): Composite Following the strategic directions proposed by the National Institute on Aging, an overall objective of the proposed research in this program project is to identify genetic and non-genetic factors and mechanisms, which can promote long and healthy life in humans on the basis of better understanding the relationships among regulators of aging, risks, of major diseases and related traits, and lifespan. This objective will be reached on the basis of integrative analyses of genome-wide SNP genotyping data and longitudinal data on life course processes in human organisms. The research in this program project will be performed in three subprojects, supported by the (A) Administrative, and (B) Data Management/Analytic Cores. We will use traditional and advanced methodologies of genetic analyses and statistical modeling, and methods of systems biology, which will be built on knowledge accumulated in the fields of aging, health, and lifespan incorporated into the integrative statistical platform. The methodological concept of the POI stands to advance paradigms of current GWAS and future association studies, using next generation sequencing, by bringing state-of-the-art methods to analyzing traits of late life that breaks new ground in the area of life-course genetics. The project will address three Specific Aims. Aim 1. Conduct comprehensive association analyses using genome-wide SNP genotyping data to identify pleiotropic and specific genetic underpinnings of lifespan, risks of major diseases, health related traits, and physiological aging changes in human body. Aim 2. Conduct analysis of up-to-date information on biological effects of pleiotropic and specific genes for SNPs discovered in Aim 1 to dissect their roles in molecular pathways, and biological processes and functions. Aim 3. Perform dynamic integration of genetic effects revealed in Aims 1 and 2 into the life course processes in individuals by combining methods of systems biology and advanced statistical modeling.

描述（由申请人提供）：综合遵循国家老龄化研究所提出的战略方向，该计划项目拟议研究的总体目标是确定可以促进长寿和健康生活的遗传和非遗传因素和机制在更好地理解衰老、风险、主要疾病和相关特征以及寿命调节因素之间的关系的基础上，对人类进行研究。这一目标将在对全基因组 SNP 基因分型数据和人类有机体生命过程过程纵向数据的综合分析的基础上实现。该计划项目的研究将在三个子项目中进行，由 (A) 管理核心和 (B) 数据管理/分析核心支持。我们将使用传统和先进的遗传分析和统计建模方法以及系统生物学方法，将其建立在老龄化、健康和寿命领域积累的知识基础上，纳入综合统计平台。 POI 的方法论概念旨在利用下一代测序，通过采用最先进的方法来分析晚年特征，从而推进当前 GWAS 和未来关联研究的范式，从而在生命历程遗传学领域。该项目将实现三个具体目标。目标 1. 使用全基因组 SNP 基因分型数据进行全面关联分析，以确定寿命、重大疾病风险、健康相关的多效性和特定遗传基础性状以及人体的生理衰老变化。目标 2. 对目标 1 中发现的 SNP 的多效性和特定基因的生物学效应的最新信息进行分析，以剖析它们在分子途径、生物过程和功能中的作用。目标 3. 通过结合系统生物学和高级统计模型的方法，将目标 1 和 2 中揭示的遗传效应动态整合到个体的生命过程中。