Role of the metabolic syndrome profile in genetic susceptibility to Alzheimer's d

代谢综合征谱在阿尔茨海默病遗传易感性中的作用 d

• 批准号: 8702571
• 负责人: Iryna Lobach
• 金额: $ 21.09万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-15 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702571
• 关键词: Accounting; Address; Age Factors; Age-associated memory impairment; Aging; Alzheimer' s Disease; Behavior; Bioinformatics; California; Central obesity; Clinical; Complex; Data Analyses; Data Set; Dependence; Disease; Education; Enrollment; Environment; Environmental Risk Factor; Epidemiologic Studies; Evaluation; Funding; Gender; Genes; Genetic; Genetic Markers; Genetic Predisposition to Disease; Genetic Structures; Genomics; Genotype; Goals; Health; High Density Lipoproteins; Human; Hyperglycemia; Hypertension; Hypertriglyceridemia; Impaired cognition; Impairment; Individual; Joints; Lead; Life Style; Literature; Memory; Metabolic; Metabolic syndrome; Methodology; Methods; Neurodegenerative Disorders; Neurologic; Obesity; Parkinson Disease; Participant; Pharmaceutical Preparations; Phenotype; Prevention; Publishing; Race; Recording of previous events; Regression Analysis; Research; Risk; Risk Factors; Role; San Francisco; Schizophrenia; Structure; Substance abuse problem; Techniques; Testing; United States; Universities; Validation; age related; base; behavioral impairment; enhancing factor; flexibility; functional disability; gene environment interaction; genetic risk factor; genome wide association study; improved; innovation; non-genetic; public health relevance; sedentary

DESCRIPTION (provided by applicant): Increasing evidence from human epidemiologic studies suggests that metabolic abnormalities are associated with age-related cognitive decline and impairment. Because obesity and sedentary lifestyle might be on rise in the United States, it is critical to elucidate the role of these modifiable behaviors on risk for cognitive decline. Alzheimer's disease (AD) is the most common progressive neurodegenerative illness that leads to severe cognitive, functional and behavioral impairments on individuals. Identifying factors that enhance one's vulnerability to AD can provide a basis for its prevention, treatment and management. A clustering of several commonly occurring disorders, including abdominal obesity, hypertriglyceridemia, low high-density lipoprotein level, hypertension and hyperglycemia define the metabolic syndrome profile. The extant literature suggests that a major vulnerability factor to AD is genetic predisposition, accounting for 60-80% of the attributable risk. A number of recent genetic and genomic studies demonstrated evidence for genetic predisposition to the metabolic syndrome profile. The goal of this proposal is to apply advanced statistical techniques to study the independent, cumulative and interactive effects of genetic and metabolic syndrome risk factors in AD. The proposed study has the potential to uncover new genetic risk factors and to better characterize role of the metabolic syndrome risk factors for AD. Another innovative feature of this project is that this methodology is flexible and can be applied to other complex diseases, such as Parkinson's, substance abuse or Schizophrenia where other large genetic and clinical datasets exist.

描述（由申请方提供）：来自人类流行病学研究的越来越多的证据表明，代谢异常与年龄相关的认知能力下降和损害有关。由于肥胖和久坐不动的生活方式在美国可能正在上升，因此阐明这些可改变的行为对认知能力下降风险的作用至关重要。阿尔茨海默病（AD）是最常见的进行性神经退行性疾病，其导致个体的严重认知、功能和行为障碍。确定那些 增强个体对AD的易感性可以为AD的预防、治疗和管理提供基础。几种常见疾病的聚集，包括腹部肥胖、高胆固醇血症、低高密度脂蛋白水平、高血压和高血糖症定义了代谢综合征特征。现有文献表明，AD的一个主要易感因素是遗传易感性，占归因风险的60-80%。最近的一些遗传和基因组研究证明了代谢综合征的遗传易感性的证据。本提案的目的是应用先进的统计技术来研究AD中遗传和代谢综合征危险因素的独立、累积和交互作用。这项研究有可能发现新的遗传风险因素，并更好地描述代谢综合征风险因素对AD的作用。该项目的另一个创新特点是，这种方法灵活， 可以应用于其他复杂的疾病，如帕金森氏症，药物滥用或精神分裂症，其中存在其他大型遗传和临床数据集。