HERITABILITY OF SLEEP HOMEOSTASIS

睡眠稳态的遗传性

基本信息

批准号：
7510341
负责人：
SAMUEL T. KUNA
金额：
$ 42.37万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7510341
关键词：
Biological Biology Breathing Breeding Complex Diagnosis Disease Dizygotic Twins Drops Electroencephalogram Electroencephalography Excessive Daytime Sleepiness Exhibits Future Genetic Goals Heritability Homeostasis Human Inbred Strains Mice Individual Individual Differences Industrial Accidents Laboratories Measures Methods Mouse Strains Numbers Patients Performance Phenotype Physiological Play Population Population Study Predisposition Prevalence Principal Investigator Process REM Sleep Range Rate Reaction Time Recovery Recruitment Activity Reporting Risk Role Sleep Sleep Apnea Syndromes Sleep Deprivation Sleep Fragmentations Societies Symptoms Testing Twin Multiple Birth Variant Vehicle crash Wakefulness base cohort density functional disability genetic variant insight non rapid eye movement pressure programs respiratory response trait vigilance

项目摘要

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的一个普遍问题，与车辆碰撞和工业事故的风险增加有关。困倦在一定程度上是由与睡眠稳态相关的基本生物学决定的，即清醒期间睡眠压力的累积率。据报道，正常受试者对睡眠剥夺的易感性存在差异，但相同睡眠时间产生的功能障碍程度存在较大的个体差异。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。这个提议是基于睡眠稳态是人类遗传特征的假设。考虑到研究睡眠稳态的表型分析的复杂性，我们建议研究同卵双胞胎和异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恢复睡眠期间 delta 功率的增加以及长时间清醒期间 theta 功率的增加来评估 80 对同卵双胞胎和 80 对异卵双胞胎的睡眠稳态。受试者将通过 PennTwins 队列进行招募，这是一个基于人群的队列，由约 1,800 对双胞胎组成。如果显示睡眠稳态的遗传性，这种基于脑电图的表型分析策略无法轻易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，我们总体策略的一部分是评估并可能验证其他表型分析方法，这些方法在生理上不太严格，但更容易应用于更多的受试者。因此，作为一个次要目标，我们还将估计长时间清醒期间表现下降的遗传性，作为评估睡眠稳态的替代方法。我们将特别确定基于异卵双胞胎之间的生理密集表型的测量差异是否反映在这种更容易执行的表型方法的差异中。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。