A KATP channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila
A KATP channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila
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DOI：
10.1038/mp.2011.142
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发表时间：
2013-01-01
影响因子：
11
通讯作者：
Roenneberg, T.
中科院分区：
文献类型：
--
作者：
Allebrandt, K. V.;Amin, N.;Roenneberg, T.
人类一生中大约有三分之一的时间在睡觉。睡眠时间长或短的人与代谢综合征和精神疾病有关，这一观察表明睡眠时间的长短是适应性的。虽然睡眠持续时间可以受到光周期（季节）和夹带阶段（时钟类型）的影响，但人类家族性睡眠障碍表明睡眠存在强烈的遗传调节。因此，我们对7个欧洲人群（N=4251）的睡眠时间进行了高密度全基因组关联研究。我们在ABCC 9基因中发现了一个内含子变异（rs 11046205; P=3.99 x 10（-8）），它解释了睡眠时间变异的大约5%。季节和时钟类型对睡眠持续时间的影响仅在重复样本（N=5949）中观察到。在复制样本的一个亚组中发现的相关性的荟萃分析，选择进入季节和时间型，以及发现结果显示了全基因组的意义。果蝇神经元中保守的ABCC 9同源物的RNA干扰敲低实验使果蝇在夜间的前3小时内失眠。ABCC 9编码ATP敏感性钾通道亚基（SUR 2），作为细胞内能量代谢的传感器。Molecular Psychiatry（2013）18，122-132; doi：10.1038/mp.2011.142; 2011年11月22日在线发表
Humans sleep approximately a third of their lifetime. The observation that individuals with either long or short sleep duration show associations with metabolic syndrome and psychiatric disorders suggests that the length of sleep is adaptive. Although sleep duration can be influenced by photoperiod (season) and phase of entrainment (chronotype), human familial sleep disorders indicate that there is a strong genetic modulation of sleep. Therefore, we conducted high-density genome-wide association studies for sleep duration in seven European populations (N=4251). We identified an intronic variant (rs11046205; P=3.99 x 10(-8)) in the ABCC9 gene that explains approximate to 5% of the variation in sleep duration. An influence of season and chronotype on sleep duration was solely observed in the replication sample (N=5949). Meta-analysis of the associations found in a subgroup of the replication sample, chosen for season of entry and chronotype, together with the discovery results showed genome-wide significance. RNA interference knockdown experiments of the conserved ABCC9 homologue in Drosophila neurons renders flies sleepless during the first 3 h of the night. ABCC9 encodes an ATP-sensitive potassium channel subunit (SUR2), serving as a sensor of intracellular energy metabolism. Molecular Psychiatry (2013) 18, 122-132; doi:10.1038/mp.2011.142; published online 22 November 2011