Relationships among Genetic Regulators of Aging Health and Lifespan

根据美国国家老龄化研究所提出的战略方向，本项目拟进行的研究的总体目标是在更好地了解衰老调节因子、重大疾病风险及相关特征与寿命之间的关系的基础上，确定促进人类健康长寿的遗传和非遗传因素和机制。这一目标将在全基因组SNP基因分型数据和人类生物体生命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)行政和(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，以及系统生物学的方法，这些方法将建立在老龄化，健康和寿命领域积累的知识基础上，并将其纳入综合统计平台。POI的方法学概念将推动当前GWAS和未来关联研究的范式，使用下一代测序，通过引入最先进的方法来分析老年生活的特征，这在老年生活中开辟了新的领域

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.