Replication of Associations of Single Nucelotide Polymor

单核苷酸多聚物关联的复制

• 批准号: 7135638
• 负责人: Jack M Guralnik
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7135638
• 关键词: aging; behavioral /social science research tag; chordate locomotion; developmental genetics; functional ability; genotype; human data; phenotype; single nucleotide polymorphism

Identifying the important SNPs in the aging pathways requires the availability of suitable phenotype measures that properly reflect the process. The traditional focus of much aging research has been on survival, and especially on extreme longevity and centenarians. However, the reported heritability of lifespan is modest - 26% for males and 23% for females. Also, it is clear that environmental factors play a strong role in survival, as genetic factors cannot explain the extraordinary rise in human longevity experienced in recent decades. In contrast to survival, certain aspects of physical functioning, notably speed of walking and standing up from the sitting position, and muscle strength in old age, appear to be highly heritable. It has reported that the heritability of performance on an 8-foot walk in the National Heart, Lung, and Blood Institute (NHLBI) Twin Study was 51%, and time to rise from a chair five times was 56%. Analysis of the association between each of 290 SNPs and reported limitation in walking or stair climbing has been done in 2000 Epic-Norfolk women used as controls in the EPIC-Norfolk Cancer Study done in the Norfolk region of England. These SNPs were in 100 genes that were selected as being candidates for cancers. Those studied include genes linked to oxidative damage, DNA repair, insulin like growth factors and cell cycle genes, all potentially related to aging outcomes as well as cancer. The phenotype was defined through responses of participants to the physical function domain of the Short-Form 36 questionnaire. Using samples from over 2000 additional women from the control group of that study, this work will attempt to replicate initial association findings by testing the link between 11 specific SNPs and reported mobility performance. Genotyping is now nearly complete and analyses are under way.

识别衰老途径中的重要 SNP 需要有合适的表型测量方法来正确反映该过程。许多衰老研究的传统焦点一直是生存，特别是极端长寿和百岁老人。然而，据报道，寿命遗传率较低——男性为 26%，女性为 23%。此外，很明显，环境因素在生存中发挥着重要作用，因为遗传因素无法解释近几十年来人类寿命的显着增长。与生存相反，身体机能的某些方面，尤其是行走速度和从坐姿站起来的速度，以及老年时的肌肉力量，似乎具有高度遗传性。据报道，美国国家心肺血液研究所 (NHLBI) 双胞胎研究中，8 英尺步行表现的遗传率为 51%，从椅子上站起来 5 次的时间遗传率为 56%。 在英格兰诺福克地区进行的 EPIC-Norfolk 癌症研究中，对 290 个 SNP 中的每一个与报告的步行或爬楼梯受限之间的关联进行了分析，研究对象为 2000 名 Epic-Norfolk 女性，这些女性用作对照。这些 SNP 存在于被选为癌症候选基因的 100 个基因中。这些研究包括与氧化损伤、DNA 修复、胰岛素样生长因子和细胞周期基因相关的基因，所有这些都可能与衰老结果以及癌症相关。表型是通过参与者对简短 36 问卷的身体功能领域的回答来定义的。这项工作将使用来自该研究对照组的 2000 多名女性样本，通过测试 11 个特定 SNP 与报告的流动性表现之间的联系来尝试复制最初的关联发现。基因分型现已接近完成，分析正在进行中。