HERITABILITY OF SLEEP HOMEOSTASIS

睡眠稳态的遗传性

• 批准号: 6716889
• 负责人: SAMUEL T. KUNA
• 金额: $ 33万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6716889
• 关键词: actigraphy; behavior test; behavioral genetics; dizygotic twins; electroencephalography; family genetics; functional ability; genetic susceptibility; homeostasis; human middle age (35-64); human subject; method development; monozygotic twins; patient oriented research; performance; phenotype; psychomotor reaction time; questionnaires; sleep; sleep apnea; sleep deprivation; wakefulness; young adult human (21-34)

Excessive daytime sleepiness is a prevalent problem in our society associated with an increased risk of vehicular crashes and industrial accidents. Sleepiness is, in part, determined by fundamental biology relating to sleep homeostasis, i.e., the rate of accumulation of the pressure for sleep during wakefulness. A differential susceptibility to sleep deprivation is reported in normal subjects with large intra-individual differences in the degree of functional impairment produced by the same duration of sleep. Genetics are likely to play an important role in sleep homeostasis as shown by recent studies in inbred mouse strains, but whether genetics plays any role in humans and, if so, the magnitude of this role, is unknown. This proposal is based on the hypothesis that sleep homeostasis is a heritable trait in humans. Given the complexity of phenotyping to study sleep homeostasis, we propose that studying differences in the variances of the phenotype between monozygotic and dizygotic twins is the optimal approach to estimate heritability of sleep homeostasis. We will assess sleep homeostasis in 80 pairs of monozygotic and 80 pairs of dizygotic twins by quantifying the increase in delta power during recovery sleep following sleep deprivation and the increase in theta power during the period of prolonged wakefulness. Subjects will be recruited using the PennTwins Cohort, a population-based cohort of about 1,800 twin pairs. If heritability of sleep homeostasis is shown, this EEG-based phenotyping strategy could not be easily applied to the larger scale population studies that will be required to assess underlying genetic variants. Thus, part of our overall strategy is to evaluate, and potentially validate, other approaches to phenotyping that are less physiologically rigorous but are more easily applied to a larger number of subjects. Therefore, as a subsidiary goal, we will also estimate heritability of performance lapses during prolonged wakefulness as a surrogate method to assess sleep homeostasis. We will particularly determine whether the differences in the measures based on our physiological intensive phenotypes between pairs of dizygotic twins are reflected in differences in this phenotyping approach that is simpler to perform. Such a result would indicate that this simpler method could be used in larger scale population studies, and will be part of future strategies to elucidate genetic variants determining sleepiness.

白天过度嗜睡是我们社会中普遍的问题，与增加车辆撞车和工业事故的风险增加有关。嗜睡部分是由与睡眠体内平衡有关的基本生物学决定的，即清醒期间睡眠压力的积累率。在正常受试者中报道了对睡眠剥夺的差异敏感性，在同一睡眠持续时间产生的功能障碍程度上具有较大的个体内差异。遗传学在睡眠稳态中可能起重要作用，如最近在近交小鼠菌株的研究所表明的那样，但是遗传学是否在人类中起任何作用，如果是的，则遗传学的大小是未知的。该提议是 基于以下假设：睡眠体内平衡是人类的遗传特征。鉴于表型研究睡眠体内平衡的复杂性，我们建议研究单卵双胞胎和双卵双胞胎之间表型方差的差异是估计睡眠稳态遗传力的最佳方法。我们将通过量化睡眠剥夺后的恢复睡眠期间的三角洲功率的增加以及在长时间的唤醒期间恢复睡眠的增加，以80对单卵双胞胎和80对双胞胎双胞胎评估睡眠体内平衡。受试者将使用Penntwins队列招募，Penntwins队列是大约1,800个双胞胎对的基于人群的队列。如果显示了睡眠体内平衡的遗传力， 这种基于脑电图的表型策略不能轻易地应用于评估基本遗传变异所需的大规模人群研究。因此，我们整体策略的一部分是评估并可能验证其他在生理上严格较少但更容易应用于较大受试者的表型的方法。因此，作为子公司目标，我们还将估计长期清醒期间性能失误的遗传力，作为评估睡眠稳态的替代方法。我们将特别确定基于我们的生理强化表型的测量差异是否反映在这种表型方法中的差异中，更简单地执行。这样的结果将表明，这种更简单的方法可以用于大规模的人群研究中，并将成为阐明决定嗜睡的遗传变异的未来策略的一部分。