Genetic Studies of Successful Aging in the Amish

阿米什人成功老龄化的遗传学研究

• 批准号: 6613193
• 负责人: William K SCOTT
• 金额: $ 56.84万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6613193
• 关键词: Mennonite; clinical research; cognition; culture; epidemiology; family genetics; functional ability; genetic screening; genotype; human subject; human very old age (85+); interview; linkage mapping; longevity; nucleic acid quantitation /detection; population survey; satisfaction; single nucleotide polymorphism; social support network

DESCRIPTION (provided by applicant): Advances in molecular and statistical methods have greatly facilitated the identification of susceptibility genes for diseases, such as Alzheimer disease, that are common in older adults. These same methods may be applied to the study of the natural aging process to identify genes that are associated with a long and healthy life. Identification of both disease-causing and health-promoting polymorphisms and their interactions with the environment has the potential to greatly improve the health of older adults, the most rapidly growing segment of the U.S. population. One method of identifying genes associated with a particular trait is to study relatively stable, isolated populations established by a few founding members, such as the Amish community in northern Indiana. This community has previously participated in a cross-sectional survey for cognitive impairment conducted from 1991-1993. Several families with multiple cognitively impaired individuals were identified and included in ongoing studies of the genetics of dementia at the DUMC Center for Human Genetics. We also observed in these families apparent clustering of "successful aging", suggesting that this trait may be, in part, under genetic control. In light of these observations, we propose a second population survey to systematically evaluate Amish adults aged 80 and older for cognitive and functional impairment. We will determine the prevalence and degree of familial aggregation of successful aging in the Amish community and perform genetic studies to identify genes associated with successful aging. To accomplish these goals, we specifically propose to: (1) conduct a community survey of Amish residents aged 80 and older in Adams and surrounding counties in Indiana and Holmes and surrounding counties in Ohio; (2) examine the relationship between successful aging and genes implicated in longevity; (3) perform a complete genomic screen for successful aging loci, and (4) follow-up results of the genomic screen through positional cloning and candidate gene analysis approaches.

描述（由申请人提供）：分子和统计方法的进步极大地促进了老年人常见疾病（如阿尔茨海默病）易感基因的鉴定。这些相同的方法可以应用于自然衰老过程的研究，以确定与长寿和健康生活相关的基因。鉴定致病和促进健康的多态性及其与环境的相互作用有可能大大改善老年人的健康，老年人是美国人口中增长最快的部分。鉴定与特定性状相关的基因的一种方法是研究由少数创始成员建立的相对稳定的孤立群体，例如北方印第安纳州的阿米什人社区。该社区以前曾参加过1991-1993年进行的认知障碍横断面调查。DUMC人类遗传学中心确定了几个有多个认知障碍个体的家庭，并将其纳入正在进行的痴呆症遗传学研究中。我们还观察到，在这些家庭中明显的集群“成功的老化”，这表明这种特性可能是，在某种程度上，遗传控制。根据这些观察结果，我们建议进行第二次人口调查，以系统地评估80岁及以上的阿米什成年人的认知和功能障碍。我们将确定在阿米什社区成功老龄化的流行率和家庭聚集的程度，并进行遗传研究，以确定与成功老龄化相关的基因。为了实现这些目标，我们特别提出：（1）对印第安纳州的亚当斯及周边县和俄亥俄州的霍姆斯及周边县的80岁及以上的阿米什居民进行社区调查;（2）检查成功衰老与长寿基因之间的关系;（3）对成功的衰老位点进行完整的基因组筛选，以及（4）通过定位克隆和候选基因分析方法对基因组筛选的结果进行随访。