Circadian rhythm genes and sleep disturbances in the elderly

老年人的昼夜节律基因与睡眠障碍

• 批准号: 7673719
• 负责人: Gregory J. Tranah
• 金额: $ 55.39万
• 依托单位: CALIFORNIA PACIFIC MED CTR RES INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7673719
• 关键词: Address; Affect; African American; Age Factors; Aging; Animal Model; Biology; Biometry; California; Candidate Disease Gene; Caring; Caucasians; Caucasoid Race; Characteristics; Circadian Rhythms; Cognition; Cognitive; Collection; Comorbidity; Complex; Consultations; DNA; Data; Data Set; Disease; Elderly; Evaluation; Funding; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Haplotypes; Health; Home environment; Human; Impaired cognition; Intervention; Lead; Longevity; Measures; Medical; Medical center; Melatonin; Mental Depression; Metabolism; Methods; Molecular Biology; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Observational Study; Outcome; Participant; Pathway interactions; Phenotype; Polysomnography; Population; Positioning Attribute; Predisposing Factor; Process; Productivity; Public Health; Quality of life; Regulation; Relative (related person); Research; Research Institute; Rest; Risk; Role; Safety; Sampling; San Francisco; Scientist; Signal Pathway; Single Nucleotide Polymorphism; Sleep; Sleep Disorders; Sleep disturbances; Stratification; Testing; Universities; Visit; Woman; Wrist; actigraphy; age group; age related; circadian pacemaker; cognitive function; cohort; cost; depression; gene discovery; gene environment interaction; genetic epidemiology; genetic variant; improved; men; mortality; novel; older men; older women; osteoporosis with pathological fracture; prospective; public health relevance

DESCRIPTION (provided by applicant): Sleep disorders among the elderly are pervasive, yet frequently undiagnosed and untreated. 'Poor sleep' has been associated with a variety of age-related conditions, including reduced cognitive function, depression and mortality. Sleep-wake regulation is a complex process involving environmental influences and genetic predisposing factors and little is known about the effect of circadian gene variants on human sleep function and age-related outcomes. This project will test the hypothesis that genetic variations in circadian pathway genes affect human sleep function and other age-related outcomes. Our specific aims are to test common genetic variants and haplotypes in 21 circadian rhythm and 4 melatonin metabolism genes for association with rest activity rhythms and sleep characteristics as measured by actigraphy, and with cognitive function, depression and mortality in two prospective cohorts of elderly U.S. women and men participating in the SOF and MrOS cohorts. During 2002-2003, wrist actigraphy was recorded in all returning Caucasian and African American SOF participants (n>2600 with DNA collected). During the MrOS sleep visit in 2004-2005, 2,846 Caucasian and African American participants (all with available DNA) completed wrist actigraphy and in-home overnight polysomnography. We are also including all African Americans with available DNA to improve our power to detect genotype associations with mortality, cognitive function and depression. This is one of the largest data sets of objective sleep data and associated mental, depression, and health data available in the world. We are uniquely positioned to examine the role of circadian rhythm and melatonin metabolism gene variants in a large sample. Compared to the cost of recruitment, phenotyping, and DNA collection, which have already been accomplished in >5700 participants, the genotyping cost will be small. The 2003 National Sleep Disorders Research Plan as put forward by The National Center on Sleep Disorders Research calls for an assessment of normal human sleep phenotypes and a full evaluation of "associated genotypes" to define the genetic underpinning of abnormal sleep or altered circadian rhythm profiles. Understanding the underlying causes and consequences of sleep disturbances and cognitive impairments is a high priority in terms of public health. Discovering gene polymorphisms that affect sleep and other age-related outcomes could lead to interventions that have a very significant impact on improving health, safety, and productivity of the elderly population. PUBLIC HEALTH RELEVANCE: This project will test whether genetic variants in the 21 circadian rhythm and 4 melatonin metabolism genes are associated with rest activity rhythms and sleep characteristics (as measured by actigraphy), mortality, cognitive function and depression in older men and women participating in the Study of Osteoporotic Fractures and Osteoporotic Fractures in Men cohorts. These are two of the largest data sets of objective sleep data and associated mental, depression, and health data available in the world and relative to the costs of recruitment and phenotyping, which have already been accomplished, the genotyping cost is small. Discovering genes that affect sleep and age-related outcomes could lead to interventions that have a very significant impact on improving health, quality of life and longevity on the elderly population.

描述（由申请人提供）：老年人之间的睡眠障碍是普遍的，但经常未经诊断和未经治疗。 “睡眠不佳”与各种与年龄相关的疾病有关，包括降低认知功能，抑郁和死亡率。睡眠效果调节是一个复杂的过程，涉及环境影响和遗传易感因素，并且对昼夜节律基因变异对人睡眠功能和与年龄相关的结果的影响知之甚少。该项目将检验以下假设：昼夜节律途径基因的遗传变异会影响人的睡眠功能和其他与年龄有关的结果。我们的具体目的是测试21种昼夜节律和4种褪黑激素代谢基因的常见遗传变异和单倍型，以通过行动术衡量的REST活性节奏和睡眠特征与参与Sof和Mros Cohorts的两个前瞻性群体中的认知功能，抑郁症和死亡率相关。在2002 - 2003年期间，所有回归的高加索和非裔美国人SOF参与者都记录了手腕动作法（收集DNA的n> 2600）。在2004年至2005年的MROS睡眠访问期间，有2,846名高加索和非裔美国人参与者（均具有可用DNA）完成了手腕精法和内室内的通宵多仪。我们还包括所有具有可用DNA的非裔美国人，以提高我们检测与死亡率，认知功能和抑郁症的基因型关联的能力。这是目标睡眠数据以及相关的心理，抑郁和健康数据的最大数据集之一。我们在大型样本中的昼夜节律节奏和褪黑激素代谢基因变体的作用是独特的。与已经在> 5700名参与者中完成的招聘，表型和DNA收集成本相比，基因分型成本将很小。国家睡眠障碍研究中心提出的2003年国家睡眠障碍研究计划要求评估正常的人类睡眠表型，并对“相关基因型”进行全面评估，以定义异常睡眠或改变昼夜节律节律特征的遗传基础。在公共卫生方面，了解睡眠障碍和认知障碍的根本原因和后果是重中之重。发现影响睡眠和其他与年龄相关的结果的基因多态性可能导致干预措施，这些干预措施对改善老年人群的健康，安全性和生产力产生非常重大的影响。公共卫生相关性：该项目将测试21种昼夜节律和4种褪黑激素代谢基因中的遗传变异是否与REST活性节奏和睡眠特征（通过行为术的衡量），死亡率，认知功能和抑郁症的老年男性和妇女的抑郁症相关，年龄较大的男性和妇女参与了骨质疏松型菌群和骨质骨骼虫的肉豆病研究。这是目标睡眠数据的两个最大数据集以及世界上可用的精神，抑郁症和健康数据，以及相对于招募和表型的成本，已经实现了，基因分型成本很小。发现影响睡眠和与年龄相关的结果的基因可能导致干预措施，这些干预措施对改善健康人群的健康，生活质量和寿命有很大的影响。