Objective and subjective measures of sleep initiation are differentially associated with DNA methylation in adolescents.
Objective and subjective measures of sleep initiation are differentially associated with DNA methylation in adolescents.
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DOI：
10.1186/s13148-023-01553-2
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发表时间：
2023-08-26
影响因子：
5.7
通讯作者：
Fernandez-Mendoza, Julio
中科院分区：
文献类型：
--
作者：
Larsen, Michael;He, Fan;Kawasawa, Yuka Imamura;Berg, Arthur;Vgontzas, Alexandros N.;Liao, Duanping;Bixler, Edward O.;Fernandez-Mendoza, Julio
青春期的开始与睡眠昼夜节律的改变有关，导致睡眠开始延迟[即睡眠开始时间较晚(SOT)]，原因是上床时间较晚和/或睡眠开始潜伏期(SOL)较长。几项全基因组关联研究(GWAS)已经确定了可能与睡眠表型的病因学有关的基因。然而，昼夜节律也是受表观遗传调控的；因此，表观遗传生物标记物可能提供青春期睡眠开始转变的生理学以及睡眠开始时间延长或延迟的病理生理学。全基因分析表明，在使用自我报告、活动描记(ACT)和多导睡眠图(PSG)的睡眠起始测量中，1818个独特基因内或大约1818个独特基因存在差异甲基化，而GWAS知情分析产生了67个基因。确定了睡前(PSG)、SOL(主观、ACT和PSG)和SOT(主观和PSG)的基因命中率。12个基因中的DNA甲基化与主观和PSG测量的SOL相关，31个基因与ACT和PSG测量的SOL相关，19个基因的DNA甲基化与主观和ACT测量的SOL相关，1个基因(SMG1P2)的甲基化位点与主观、ACT和PSG测量的SOL相关。目的和主观的青少年睡眠启动与先前在成人睡眠和昼夜表型中发现的基因的DNA甲基化改变有关。此外，我们的数据为习惯性(主观和ACT)SOL和实验室内SOT以及参与昼夜节律(即RASD1、RAI1)、心脏代谢紊乱(即FADS1、WNK1、SLC5A6)和神经精神障碍(即PRR7、SDK1、FAM172A)的基因及其周围的DNA甲基化提供了潜在的表观遗传学联系。如果得到验证，这些部位可能为早期发现和预防涉及SOT延长或延迟的疾病提供有价值的靶点，如失眠、睡眠相延迟及其共病。网上版载有补充材料，可在10.1186/s13148023-01553-2查阅。
The onset of puberty is associated with a shift in the circadian timing of sleep, leading to delayed sleep initiation [i.e., later sleep onset time (SOT)] due to later bedtimes and/or longer sleep onset latency (SOL). Several genome-wide association studies (GWAS) have identified genes that may be involved in the etiology of sleep phenotypes. However, circadian rhythms are also epigenetically regulated; therefore, epigenetic biomarkers may provide insight into the physiology of the pubertal sleep onset shift and the pathophysiology of prolonged or delayed sleep initiation. The gene-wide analysis indicated differential methylation within or around 1818 unique genes across the sleep initiation measurements using self-report, actigraphy (ACT), and polysomnography (PSG), while GWAS-informed analysis yielded 67 genes. Gene hits were identified for bedtime (PSG), SOL (subjective, ACT and PSG) and SOT (subjective and PSG). DNA methylation within 12 genes was associated with both subjective and PSG-measured SOL, 31 with both ACT- and PSG-measured SOL, 19 with both subjective and ACT-measured SOL, and one gene (SMG1P2) had methylation sites associated with subjective, ACT- and PSG-measured SOL. Objective and subjective sleep initiation in adolescents is associated with altered DNA methylation in genes previously identified in adult GWAS of sleep and circadian phenotypes. Additionally, our data provide evidence for a potential epigenetic link between habitual (subjective and ACT) SOL and in-lab SOT and DNA methylation in and around genes involved in circadian regulation (i.e., RASD1, RAI1), cardiometabolic disorders (i.e., FADS1, WNK1, SLC5A6), and neuropsychiatric disorders (i.e., PRR7, SDK1, FAM172A). If validated, these sites may provide valuable targets for early detection and prevention of disorders involving prolonged or delayed SOT, such as insomnia, delayed sleep phase, and their comorbidity. The online version contains supplementary material available at 10.1186/s13148-023-01553-2.
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影响因子：
10.5
作者：
de Zambotti M;Goldstone A;Colrain IM;Baker FC
通讯作者：
Baker FC
影响因子：
4.6
作者：
He, Fan;Berg, Arthur;Liao, Duanping
通讯作者：
Liao, Duanping
影响因子：
3.5
作者：
Gaine ME;Chatterjee S;Abel T
通讯作者：
Abel T
影响因子：
3.7
作者：
Clarkson-Townsend, Danielle A.;Everson, Todd M.;Marsit, Carmen J.
通讯作者：
Marsit, Carmen J.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y