Objective and subjective measures of sleep initiation are differentially associated with DNA methylation in adolescents.

IF 5.7 2区 医学 Q1 Medicine
Michael Larsen, Fan He, Yuka Imamura Kawasawa, Arthur Berg, Alexandros N Vgontzas, Duanping Liao, Edward O Bixler, Julio Fernandez-Mendoza
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引用次数: 0

Abstract

Introduction: 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.

Results: 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.

Conclusions: 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.

Abstract Image

Abstract Image

在青少年中,睡眠开始的客观和主观测量与DNA甲基化存在差异。
青春期的开始与昼夜睡眠时间的变化有关,由于就寝时间较晚和/或睡眠开始潜伏期(SOL)较长,导致睡眠开始延迟[即睡眠开始时间(SOT)较晚]。一些全基因组关联研究(GWAS)已经确定了可能参与睡眠表型病因学的基因。然而,昼夜节律也受表观遗传调控;因此,表观遗传生物标志物可以为青春期睡眠开始转移的生理学和睡眠开始时间延长或延迟的病理生理学提供见解。结果:基因范围的分析表明,在使用自我报告、活动描记(ACT)和多导睡眠描记(PSG)进行的睡眠开始测量中,1818个独特基因内部或周围存在差异甲基化,而gwas的分析产生了67个基因。在就寝时间(PSG)、SOL(主观、ACT和PSG)和SOT(主观和PSG)中发现基因命中。12个基因的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。结论:青少年客观和主观睡眠起始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SOT以及参与昼夜节律调节的基因(即RASD1, RAI1),心脏代谢疾病(即FADS1, WNK1, SLC5A6)和神经精神疾病(即PRR7, SDK1, FAM172A)中及其周围的DNA甲基化之间的潜在表观遗传联系提供了证据。如果得到证实,这些位点可能为早期发现和预防涉及延长或延迟SOT的疾病提供有价值的靶点,如失眠、睡眠阶段延迟及其合并症。
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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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