PACIFIC GENETIC EPIDEMIOLOGIC STUDY ON AGING

描述：（申请摘要）流行病学、家庭和双胞胎 研究表明，相当大比例的表型变异， 长寿和功能能力是遗传的。 一个可能的解释是 对代谢途径有重要影响的单基因多态性 可能有助于一些慢性疾病的潜在发病机制， 老化过程和老化过程同时进行。 为了探索这个假设， 以及衰老遗传学的其他领域，我们建议发起， 建立一个新的遗传网络[太平洋遗传网络]， 遗传学、流行病学、老年病学、生物统计学和 来自夏威夷大学库阿基尼医学中心的环境科学， 斯坦福大学皇后医学中心和太平洋健康研究 院 该网络将以檀香山的现有要素为基础 心脏计划（HHP），一项针对老年日裔美国人的流行病学研究， 家庭血压计划，一项多中心的遗传学研究， 高血压 它将计划和实施全面的遗传流行病学 利用候选基因/遗传关联分析的衰老研究 的设计. 在第一阶段，我们将展示这个网络的能力， 研究与长寿和维持 在基于人口的样本中的功能能力。 利用单核苷酸 多态性（SNPs）和与表型数据相关的现有HHP DNA样本 根据35年来测量的握力和其他因素，我们将确定5个 6个线粒体和细胞核候选基因中的每一个的高频率SNP (30 SNP）。将根据生物学知识选择候选基因 家庭血压计划，一项多中心的遗传学研究， 高血压 它将计划和实施全面的遗传流行病学 利用候选基因/遗传关联分析的衰老研究 的设计. 在第一阶段，我们将展示这个网络的能力， 研究与长寿和维持 在基于人口的样本中的功能能力。 利用单核苷酸 多态性（SNPs）和与表型数据相关的现有HHP DNA样本 根据35年来测量的握力和其他因素，我们将确定5个 6个线粒体和细胞核候选基因中的每一个的高频率SNP (30 SNP）。将根据生物学知识选择候选基因 将它们与能量稳态和/或产生/解毒联系起来 氧自由基，尤其是线粒体遗传变异。分型 将为30个SNP中的每一个开发检测方法， 在1997-1999年检查的1，953名老年人中进行了基因分型。 我们将 还招募了HHP队列的100名家庭成员（年龄55岁， 以上）。 在该样本中，我们将试点测试表型措施，包括 为将来的研究提供基于性能的身体功能测量。 利用 HPP数据，我们将探索创新的分析方法，如分位数 处理人口变化率数据的回归方法， 生存表型及其相关基因。 在该第一 PacGen网络将制定并提交更多的建议， 综合遗传流行病学研究（II期）。

DESCRIPTION: (Abstract from application) Epidemiological, family, and twin studies suggest that a substantial proportion of the phenotypic variation in longevity and functional ability is genetic. One possible explanation is that polymorphisms of single genes with important effects on a metabolic pathway may contribute to the underlying pathogenesis of a number of chronic conditions and the aging process simultaneously. To explore this hypothesis, as well as other areas in the genetics of aging, we propose to initiate and develop a new genetic network [the Pacific Genetic (PacGen) Network] of experts in genetics, epidemiology, geriatrics, biostatistics and environmental science from the University of Hawaii, Kuakini Medical Center, Queen's Medical Center, Stanford University and the Pacific Health Research Institute. The Network will be based on existing elements of the Honolulu Heart Program (HHP), an epidemiologic study of elderly Japanese Americans and the Family Blood Pressure Program, a multi-center study of the genetics of hypertension. It will plan and carryout comprehensive genetic epidemiologic studies in aging utilizing candidate gene/genetic association analysis designs. In Phase I, we will demonstrate the ability of this network to investigate genetic factors associated with longevity and maintenance of functional ability in a population based sample. Utilizing single nucleotide polymorphisms (SNPs) and existing HHP DNA samples linked with phenotypic data on grip strength and other factors measured over 35 years, we will identify 5 high frequency SNPs in each of 6 mitochondrial and nuclear candidate genes (30 SNPs). Candidate genes will be selected based on biologic knowledge the Family Blood Pressure Program, a multi-center study of the genetics of hypertension. It will plan and carryout comprehensive genetic epidemiologic studies in aging utilizing candidate gene/genetic association analysis designs. In Phase I, we will demonstrate the ability of this network to investigate genetic factors associated with longevity and maintenance of functional ability in a population based sample. Utilizing single nucleotide polymorphisms (SNPs) and existing HHP DNA samples linked with phenotypic data on grip strength and other factors measured over 35 years, we will identify 5 high frequency SNPs in each of 6 mitochondrial and nuclear candidate genes (30 SNPs). Candidate genes will be selected based on biologic knowledge linking them with energy homeostasis and/or the generation/detoxification of oxygen free radicals, especially mitochondrial genetic variation. Genotyping assays will be developed for each of the 30 SNPs and each SNP will be genotyped in the 1,953 elderly individuals examined in 1997-1999. We will also recruit a sample of 100 family members of the HHP cohort (ages 55 and above). In that sample we will pilot test phenotypic measures including performance based measures of physical function for future studies. Utilizing HPP data we will explore innovative analytical approaches such as quantile regression methods for dealing with population rate of change data and survival phenotypes and the genes associated with them. During this first phase the PacGen Network will develop and submit proposals for more comprehensive genetic epidemiologic studies (Phase II).