GENES AND OTHER FACTORS AFFECTING HEALTH TRAITS: EFFECTS O NAGING AND LIFESPAN

项目3 发达国家社会面临的一个新问题是延长健康寿命。 生物学和遗传学专家认为，该领域的重大突破可以通过以下方式实现 揭示了可能与晚年健康调节有关的遗传变异。一个难题 晚期生命的特征并不是直接进化选择的结果， 生物体在异质环境中与生命过程相关的过程， 基因对晚年特征的复杂作用谱。分析这种复杂性的作用， 遗传效应不是全基因组关联研究（GWAS）的主流。的目标 该子项目旨在确定人类主要疾病的遗传基础和最近的相关特征， 使用最先进的方法解决生命过程相关过程在生命周期中的作用， 生物在异质环境中塑造遗传关联，并动态整合 揭示的等位基因变异转化为个体生命过程中与健康相关的变化。这 具有挑战性的目标需要一个丰富的数据，生命过程中的健康相关的过程评估， 心脏病研究（FHS），社区动脉粥样硬化风险研究（ARIC）， 心血管健康研究（CHS），动脉粥样硬化的多种族研究（梅萨），晚发性 阿尔茨海默病家族研究（LOADFS），健康和退休调查（HRS），以及长期 生活家庭研究（LLFS）。目标1.揭示了与遗传变异相关的定量表型， 使用FHS，ARIC， CHS和梅萨。目标二。利用基因芯片揭示与重大人类疾病风险相关的遗传变异 FHS、ARIC、CHS、梅萨、HRS和LOADFS。目标3：阐明揭示的等位基因的作用 变量的寿命和进行动态集成。目标4。剖析基因的生物学作用， 揭示SNP并构建整合的变体。 相关性（参见说明）： 该项目直接处理与公共卫生有内在关联的问题，包括 对遗传易感性的医疗并发症和副作用的关注，由于复杂的 基因对健康特征的作用的性质以及对这些基因是否可以被认为是早期的关注 由于预防性干预措施在2010 - 2011年期间健康变化中的重要作用， 个人的生命历程。

Project 3 An emerging problem for societies in developed countries is extending years of healthy life. Specialists in biology and genetics argue that major breakthrough in the field can be achieved by revealing genetic variants which can be involved in regulation of health in late life. A puzzling problem is that traits of late life are not the result of direct evolutionary selection that reinforces the role of life-course-related processes in an organism in heterogeneous environment which contribute to a complex spectrum of actions of genes on traits of late life. Analysis of the role of this complexity in genetic effects is not in mainstream of genome-wide association studies (GWAS). The objective of this subproject is to identify genetic underpinnings of major human diseases and related traits of late life using state-of-the-art methods addressing the role of life-course-related processes in an organism shaping genetic associations in heterogeneous environment and to dynamically integrate the revealed allelic variants into the individuals' health-related changes during life course. This challenging goal requires a rich data on the life course health-related processes assessed in the Framingham Heart Study (FHS), the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), the Multi-Ethnic Study of Atherosclerosis (MESA), the Late Onset Alzheimer's Disease Family Study (LOADFS), the Health and Retirement Survey (HRS), and the Long Life Family Study (LLFS). Aim 1. Reveal genetic variants associated with quantitative phenotypes of physiological health given time-repeated observations for the same individuals using the FHS, ARIC, CHS, and MESA. Aim 2. Reveal genetic variants associated with risks of major human diseases using the FHS, ARIC, CHS, MESA, HRS, and LOADFS. Aim 3. Elucidate the role of the revealed allelic variants in lifespan and conduct dynamic integration. Aim 4. Dissect biological role of genes for the revealed SNPs and construct integrated variants. RELEVANCE (See instructions): This project directly addresses concerns which are of inherent relevance to public health including concern on genetic predisposition to medical complications and side-effects as a result of complex nature of gene action on health traits and concern on whether such genes can be considered as eariy life targets for preventive interventions as a result of their important role in health changes during the individuals' life course.