HERITABILITY OF SLEEP HOMEOSTASIS

在我们的社会中，白天过度嗜睡是一个普遍存在的问题，与车祸和工业事故的风险增加有关。在某种程度上，嗜睡是由与睡眠稳态有关的基本生物学决定的，即在清醒时睡眠压力的积累速度。据报道，正常受试者对睡眠剥夺的易感性存在差异，相同睡眠时间所产生的功能损害程度存在较大的个体内差异。最近对近亲繁殖小鼠品系的研究表明，基因可能在睡眠稳态中发挥重要作用，但基因是否在人类中发挥作用，如果有的话，这种作用的程度是未知的。这个建议是

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.