Laboratory of Systems Genetics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Drexel University College of Medicine, Philadelphia, PA, USA.
Sci Rep. 2024 Jan 2;14(1):260. doi: 10.1038/s41598-023-50552-z.
Sleep latency, the amount of time that it takes an individual to fall asleep, is a key indicator of sleep need. Sleep latency varies considerably both among and within species and is heritable, but lacks a comprehensive description of its underlying genetic network. Here we conduct a genome-wide association study of sleep latency. Using previously collected sleep and activity data on a wild-derived population of flies, we calculate sleep latency, confirming significant, heritable genetic variation for this complex trait. We identify 520 polymorphisms in 248 genes contributing to variability in sleep latency. Tests of mutations in 23 candidate genes and additional putative pan-neuronal knockdown of 9 of them implicated CG44153, Piezo, Proc-R and Rbp6 in sleep latency. Two large-effect mutations in the genes Proc-R and Piezo were further confirmed via genetic rescue. This work greatly enhances our understanding of the genetic factors that influence variation in sleep latency.
睡眠潜伏期，即个体入睡所需的时间，是睡眠需求的一个关键指标。睡眠潜伏期在不同物种和个体之间差异很大，具有遗传性，但缺乏对其潜在遗传网络的全面描述。在这里，我们对睡眠潜伏期进行了全基因组关联研究。利用先前在一个野生来源的果蝇群体中收集的睡眠和活动数据，我们计算了睡眠潜伏期，证实了这个复杂特征具有显著的遗传可变性。我们在 248 个基因中鉴定出了 520 个与睡眠潜伏期变异性相关的多态性。对 23 个候选基因的突变测试以及对其中 9 个的额外推定全神经元敲低实验表明，CG44153、Piezo、Proc-R 和 Rbp6 与睡眠潜伏期有关。Proc-R 和 Piezo 这两个基因中的两个大效应突变进一步通过遗传挽救得到了证实。这项工作极大地提高了我们对影响睡眠潜伏期变异的遗传因素的理解。
