Circadian and Genetic Evaluation of Extreme Sleep Timing

极端睡眠时间的昼夜节律和遗传评估

• 批准号: 7092779
• 负责人: Jeanne F Duffy
• 金额: $ 31.5万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-14 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7092779
• 关键词: adolescence (12-20); behavioral /social science research tag; behavioral genetics; biological clocks; biotechnology; blood tests; body temperature; circadian rhythms; clinical research; genetic screening; genetic susceptibility; human genetic material tag; human subject; melatonin; monitoring device; neurogenetics; polysomnography; preference; questionnaires; sleep; sleep disorders; wakefulness; young adult human (21-34); adolescence (12-20); behavioral /social science research tag; behavioral genetics; biological clocks; biotechnology; blood tests; body temperature; circadian rhythms; clinical research; genetic screening; genetic susceptibility; human genetic material tag; human subject; melatonin; monitoring device; neurogenetics; polysomnography; preference; questionnaires; sleep; sleep disorders; wakefulness; young adult human (21-34)

DESCRIPTION (provided by applicant): Although humans prefer to be active during the day and to sleep at night, diurnal preference ("morningness-eveningness") is highly variable in the population and influenced by many factors. Recently, variations in circadian rhythmicity associated with moderate diurnal preference have been reported. Individuals with extreme diurnal preference (definite morning and evening types) often have an inability to sleep and/or wake at their desired times, and such misalignment between sleep timing and the 24-h social and physical environment can lead to the circadian rhythm sleep disorders Advanced or Delayed Sleep Phase Syndrome (ASPS, DSPS). In the past decade, the genetic basis of circadian rhythmicity has been well-established, including identification of "clock" genes that comprise the molecular mechanism for the generation of circadian rhythms. Because of the relationship between circadian rhythms and diurnal preference, and the established genetic regulation of the circadian system in animals, there is likely to be a genetic basis to extreme diurnal preference and the circadian rhythm sleep disorders. There are reports of associations between diurnal preference and polymorphisms in clock genes, and reports of clock gene alterations in patients with ASPS and DSPS, although not all studies agree. These discrepancies may be due to the phenotyping methods used in those studies. Much remains unknown about the chronobiologic and sleep mechanisms, as well as the genetic basis, of these phenotypes. Here we propose a thorough phenotypic and genetic evaluation of extreme diurnal types to determine the underlying chronobiologic and genetic basis of human diurnal preference, thereby linking specific genes with observable behavior. A careful evaluation of the endogenous circadian phase (Specific Aim 1), period (Specific Aim 2), and pattern of sleep propensity (Specific Aim 3), using well-established methods (constant routine and forced desynchrony protocols) is likely to yield distinct phenotypic groups exhibiting trait-like behaviors? Genetic analysis of extreme diurnal types (Specific Aim 4) may identify associated polymorphisms in clock genes. These data should provide better understanding of the chronobiologic and genetic basis of extreme diurnal preference, leading to better treatments for circadian rhythm sleep disorders.

描述（由申请人提供）：尽管人类宁愿白天活跃，而晚上睡觉，但昼夜偏爱（“早晨 - 耐用性”）在人群中差异很大，受许多因素的影响。最近，已经报道了与中度昼夜偏好相关的昼夜节律变化。具有极端昼夜偏好（确定的早晨和晚上类型）的人通常无法在所需的时间睡觉和/或醒来，而睡眠时间与24小时社交和身体环境之间的这种不对对准会导致昼夜节律睡眠障碍高级或延迟的睡眠期综合征（ASP，DSP）。在过去的十年中，昼夜节律的遗传基础已经建立了良好的建立，包括鉴定“时钟”基因，这些基因构成了产生昼夜节律的分子机制。由于昼夜节律与昼夜偏好之间的关系，以及动物昼夜节律系统的遗传调节，因此可能存在遗传基础，以极端的昼夜偏好和昼夜节律节奏睡眠障碍。有报道说，时钟基因中的昼夜偏好与多态性之间存在关联，以及ASP和DSP患者的时钟基因改变的报道，尽管并非所有研究都同意。这些差异可能是由于这些研究中使用的表型方法。这些表型的时间生物学和睡眠机制以及遗传基础仍然未知。在这里，我们提出了对极端昼夜类型的彻底表型和遗传评估，以确定人类昼夜偏好的基本时间生物学和遗传基础，从而将特定基因与可观察到的行为联系起来。仔细评估内源性昼夜节相（特定目标1），周期（特定目标2）和睡眠倾向的模式（特定目标3），使用良好的方法（恒定的常规和强制性脱节方案）可能会产生不同的表型基团，表现出表现出类似性状的行为？极端昼夜类型的遗传分析（特定目标4）可以鉴定时钟基因中相关的多态性。这些数据应更好地了解极端昼夜偏爱的时间生物学和遗传基础，从而更好地治疗昼夜节律睡眠障碍。