Association Analysis of SNPs in Longevity Assurance Genes

长寿保证基因中SNP的关联分析

• 批准号: 7479141
• 负责人: YOUSIN SUH
• 金额: $ 33.89万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7479141
• 关键词: Accounting; Address; Affect; Age; Aging; American; Apoptosis; Attention; Biological; Biological Assay; Blood; Candidate Disease Gene; Cell Aging; Cell Proliferation; Cells; Characteristics; Classification; Clinical; Code; DNA; Databases; Disease regression; Early Diagnosis; Elderly; European; Gene Targeting; Genes; Genetic Markers; Genetic Variation; Genome; Genomic Instability; Haplotypes; Human; Human Genome Project; Individual; Individual Differences; Inherited; Intervention; Knock-in Mouse; Lead; Link; Longevity; Longitudinal Studies; Maintenance; Measures; Mexican Americans; Mutagens; Nucleotides; Pathway interactions; Phenotype; Population; Population Study; Prevention; Promoter Regions; Quality of life; Rate; Resources; Risk; Rodent; Role; Sampling; Screening procedure; Sequence Analysis; Severities; Single Nucleotide Polymorphism; Structural Models; Testing; Time; Variant; age related; aging population; base; cohort; functional decline; gene function; genetic association; healthy aging; improved; insight; middle age; multidisciplinary; novel; programs; response; trait

DESCRIPTION (provided by applicant): With the completion of the human genome project, attention is shifting towards individual genetic variation. Such variation, most of which consists of single nucleotide polymorphisms (SNPs), may account for a substantial portion of human individual phenotypic variation, including differences in aging-related characteristics. Especially important are SNPs that affect the function of genes in candidate longevity assurance pathways, since they could provide novel targets for the early detection and possible prevention of aging-related functional decline. Optimal study populations in this respect are those in which aging related phenotypes can be defined in terms of their progression from middle age onwards, rather than as snapshots in time. We hypothesize that genetic variation at loci involved in genome maintenance can be related to individual differences in the rate and severity of aging. To address this hypothesis, a systematic multidisciplinary study is proposed in which SNP haplotypes of about 100 genes in 5 genome maintenance pathways will be determined in individuals of an ongoing longitudinal study of 586 Mexican American (MA) and 428 European American (EA) (SALSA; San Antonio Longitudinal Study of Aging). Subsequent association analysis in conjunction with functional assays of allelic gene variants will provide insight into their biological significance. The results should lead to increased understanding of the role of genome maintenance in healthy aging and provide genetic markers to identify individuals at risk for specific aging related phenotypes. This will open up the possibility of targeted and personalized intervention strategies, ultimately leading to improved quality of life of the elderly population.

描述（由申请人提供）：随着人类基因组项目的完成，注意力正在转移到个体遗传​​变异。这种变异大多是由单核苷酸多态性（SNP）组成的，可能是人类个体表型变异的很大一部分，包括与衰老相关的特征的差异。尤其重要的是影响基因在候选寿命保证途径中功能的SNP，因为它们可以为早期检测和可能预防与衰老相关的功能下降提供新的目标。在这方面，最佳研究人群是可以从中年开始的发展，而不是随时间的快照来定义与衰老相关的表型的人群。我们假设基因组维持涉及的基因座的遗传变异可能与衰老率和严重程度的个体差异有关。为了解决这一假设，提出了一项系统的多学科研究，其中将在正在进行的586个墨西哥裔美国人（MA）和428欧洲裔美国人（EA）的纵向研究中确定5个基因组维持途径中约100个基因的SNP单倍型（SALSA； SANONIO纵向研究）。随后的关联分析与等位基因变体的功能测定法相结合，将洞悉其生物学意义。结果应导致人们对基因组维持在健康衰老中的作用的了解增加，并提供遗传标记，以识别患有特定衰老相关表型风险的个体。这将为有针对性和个性化的干预策略的可能性开辟了可能性，最终导致老年人口的生活质量改善。