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

作者：Michael Larsen, Fan He, Yuka Imamura Kawasawa, Arthur Berg, Alexandros N. Vgontzas, Duanping Liao, Edward O. Bixler, Julio Fernández‐Mendoza · 发表于：Clinical Epigenetics · 年份：2023 · DOI：10.1186/s13148-023-01553-2 · 被引用次数：12 · 研究领域：Sleep and related disorders、Sleep and Wakefulness Research、Circadian rhythm and melatonin

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...