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.

过度的白天嗜睡是我们社会中的一个普遍问题，与车祸和工业事故的风险增加有关。嗜睡部分地由与睡眠稳态相关的基础生物学决定，即，在清醒状态下睡眠压力的累积速率。据报道，正常受试者对睡眠剥夺的敏感性不同，相同睡眠时间产生的功能障碍程度存在较大的个体内差异。最近对近交系小鼠的研究表明，遗传学可能在睡眠稳态中发挥重要作用，但遗传学是否在人类中发挥作用，如果是的话，这种作用的大小尚不清楚。这项建议是 基于睡眠稳态是人类遗传特征的假设。鉴于研究睡眠稳态表型的复杂性，我们建议研究单卵双胞胎和双卵双胞胎之间的表型方差的差异是估计睡眠稳态遗传力的最佳方法。我们将评估80对同卵双胞胎和80对异卵双胞胎的睡眠稳态，通过量化睡眠剥夺后恢复睡眠期间δ功率的增加和长时间清醒期间θ功率的增加。受试者将使用PennTwins队列招募，这是一个基于人群的队列，约有1，800对双胞胎。如果睡眠稳态具有遗传性， 这种基于EEG的表型分析策略不能容易地应用于评估潜在遗传变异所需的更大规模的群体研究。因此，我们的整体策略的一部分是评估，并可能验证，其他方法的表型，是不太严格的生理，但更容易适用于大量的主题。因此，作为一个辅助目标，我们还将估计在长时间清醒期间表现失误的遗传性，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双卵双胞胎对之间的生理密集表型的测量的差异是否反映在这种更容易执行的表型分型方法的差异中。这样的结果表明，这种更简单的方法可以用于更大规模的人群研究，并将成为未来阐明决定嗜睡的遗传变异的策略的一部分。