Candidate Genes and Longitudinal Diability Phenotypes

候选基因和纵向残疾表型

• 批准号: 7100527
• 负责人: Jama L Purser
• 金额: $ 13.52万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7100527
• 关键词: balance; clinical research; functional ability; gait; gene expression; gene frequency; genetic screening; genotype; human data; human genetic material tag; human old age (65+); human population genetics; limb movement; longitudinal human study; performance; person with disability; sarcopenia; single nucleotide polymorphism

DESCRIPTION (provided by applicant): The candidate, Jama L. Purser, PT, MS, PhD, is an Epidemiologist with degrees in Physical Therapy and Movement Science. Her doctoral and post-doctoral training focused on trajectories of disability in aging populations. She now proposes to add a genetic component to her training, including coursework and mentorship in genetics, proteomics, and Bayesian statistics. Her long-term goal is to become an independent investigator in a new area of disablement research, focusing on observational studies of the genetic epidemiology of sarcopenia, physical performance and disability as well as clinical studies of genomic and proteomic medicine. Recent work suggests that genotypic variation may contribute to phenotypic patterns of sarcopenia, physical performance and disability among older adults, and that such genetic influence may operate through biological pathways independent of, or complementary to, the effects of disease and comorbidity. These pathways are not yet fully understood. While recent work has focused on static, disease-based phenotypes identified at a single time point, few studies have evaluated candidate gene effects on dynamic trajectories of sarcopenia, physical performance and disability over time. The specific aim is to investigate longitudinal disability-related phenotypes and their association with hypothesized genetic mechanisms (e.g. insulin-signaling, calcium channel function, and osmotic regulation). Candidate genes from several biological pathways will be studied, focusing on those potentially related to sarcopenia and physical frailty of aging. Two cohorts will be used: 1) the Duke Established Populations for Epidemiologic Studies of the Elderly (n=1757), a geographically representative sample (age 65-105, followed for 10 years), and 2) the Health, Aging and Body Composition Study (n=3,075), a random sample of community residents (age 70-79, followed for 6 years). The Duke EPESE cohort includes physical performance and disability phenotypes; the Health ABC dataset includes longitudinal muscle mass, sarcopenia and physical performance. Evaluated findings will improve public health understanding of the etiology of physical frailty. Results should also indicate directions for further disability-related genetic studies and interventions.

描述（由申请人提供）：候选人Jama L. Purser，PT，MS，PhD是一名具有物理治疗和运动科学学位的流行病学家。她的博士和博士后培训的重点是衰老人群的残疾轨迹。她现在建议在培训中增加遗传成分，包括遗传学，蛋白质组学和贝叶斯统计的课程工作和指导。她的长期目标是成为一个新的残疾研究领域的独立研究者，重点是对肌肉减少症，身体性能和残疾遗传流行病学的观察性研究以及基因组和蛋白质组学医学的临床研究。最近的工作表明，基因型变异可能有助于老年人的肌肉减少症，身体表现和残疾的表型模式，并且这种遗传影响可能通过与疾病和合并症的影响无关或互补的生物学途径来起作用。这些途径尚未完全理解。尽管最近的工作集中在一个时间点上确定的静态，基于疾病的表型，但很少有研究评估了候选基因对肌肉减少症动态轨迹的影响，随着时间的推移，身体性能和残疾。具体的目的是研究与纵向残疾相关的表型及其与假设的遗传机制（例如胰岛素信号，钙通道功能和渗透调节）的关联。将研究来自几种生物途径的候选基因，重点是与肌肉减少症和衰老的身体脆弱有关的候选基因。将使用两个队列：1）杜克大学成立了老年人的流行病学研究人群（n = 1757），一种地理位置代表性的样本（65-105岁，随后是10年），而2）健康，衰老和身体组成研究（n = 3,075）（n = 3,075），随机样本，是社区居民的随机样本（年龄在70-79岁之间）。杜克·埃皮斯（Duke Epese）队列包括身体表现和残疾表型。健康ABC数据集包括纵向肌肉质量，肌肉减少症和身体表现。评估的发现将提高公共健康对身体虚弱的病因的理解。结果还应指示进一步的残疾遗传研究和干预措施的方向。