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影响睡眠和神经疾病的多效性遗传效应。

Pleiotropic genetic effects influencing sleep and neurological disorders.

作者信息

Veatch Olivia J, Keenan Brendan T, Gehrman Philip R, Malow Beth A, Pack Allan I

机构信息

Department of Neurology, Vanderbilt University, Nashville, TN, USA; Center for Sleep and Circadian Neurobiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Center for Sleep and Circadian Neurobiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

出版信息

Lancet Neurol. 2017 Feb;16(2):158-170. doi: 10.1016/S1474-4422(16)30339-8.

Abstract

Research evidence increasingly points to the large impact of sleep disturbances on public health. Many aspects of sleep are heritable and genes influencing traits such as timing, EEG characteristics, sleep duration, and response to sleep loss have been identified. Notably, large-scale genome-wide analyses have implicated numerous genes with small effects on sleep timing. Additionally, there has been considerable progress in the identification of genes influencing risk for some neurological sleep disorders. For restless legs syndrome, implicated variants are typically in genes associated with neuronal development. By contrast, genes conferring risk for narcolepsy function in the immune system. Many genetic variants associated with sleep disorders are also implicated in neurological disorders in which sleep abnormalities are common; for example, variation in genes involved in synaptic homoeostasis are implicated in autism spectrum disorder and sleep-wake control. Further investigation into pleiotropic roles of genes influencing both sleep and neurological disorders could lead to new treatment strategies for a variety of sleep disturbances.

摘要

研究证据越来越多地表明睡眠障碍对公众健康有重大影响。睡眠的许多方面是可遗传的,并且已经确定了影响诸如睡眠时间、脑电图特征、睡眠时长以及对睡眠剥夺反应等性状的基因。值得注意的是,大规模全基因组分析已经发现了许多对睡眠时间有微小影响的基因。此外,在确定影响某些神经睡眠障碍风险的基因方面也取得了相当大的进展。对于不宁腿综合征,相关变体通常存在于与神经元发育相关的基因中。相比之下,赋予发作性睡病风险的基因在免疫系统中发挥作用。许多与睡眠障碍相关的基因变体也与常见睡眠异常的神经疾病有关;例如,参与突触稳态的基因变异与自闭症谱系障碍和睡眠-觉醒控制有关。对影响睡眠和神经疾病的基因的多效性作用进行进一步研究,可能会为各种睡眠障碍带来新的治疗策略。

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