PMID- 37634000 OWN - NLM STAT- MEDLINE DCOM- 20230828 LR - 20231121 IS - 1868-7083 (Electronic) IS - 1868-7075 (Print) IS - 1868-7075 (Linking) VI - 15 IP - 1 DP - 2023 Aug 26 TI - Objective and subjective measures of sleep initiation are differentially associated with DNA methylation in adolescents. PG - 136 LID - 10.1186/s13148-023-01553-2 [doi] LID - 136 AB - 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. CI - (c) 2023. BioMed Central Ltd., part of Springer Nature. FAU - Larsen, Michael AU - Larsen M AD - Sleep Research and Treatment Center, Department of Psychiatry & Behavioral Health, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. FAU - He, Fan AU - He F AD - Department of Public Health Sciences, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. FAU - Kawasawa, Yuka Imamura AU - Kawasawa YI AD - Departments of Biochemistry and Molecular Biology and Pharmacology, Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. FAU - Berg, Arthur AU - Berg A AD - Department of Public Health Sciences, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. FAU - Vgontzas, Alexandros N AU - Vgontzas AN AD - Sleep Research and Treatment Center, Department of Psychiatry & Behavioral Health, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. FAU - Liao, Duanping AU - Liao D AD - Department of Public Health Sciences, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. FAU - Bixler, Edward O AU - Bixler EO AD - Sleep Research and Treatment Center, Department of Psychiatry & Behavioral Health, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. FAU - Fernandez-Mendoza, Julio AU - Fernandez-Mendoza J AD - Sleep Research and Treatment Center, Department of Psychiatry & Behavioral Health, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. jfmendoza@psu.edu. LA - eng GR - R01 MH118308/MH/NIMH NIH HHS/United States GR - R01 HL136587/HL/NHLBI NIH HHS/United States GR - R01 HL063772/HL/NHLBI NIH HHS/United States GR - R01 HL097165/HL/NHLBI NIH HHS/United States GR - UL1 TR000127/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20230826 PL - Germany TA - Clin Epigenetics JT - Clinical epigenetics JID - 101516977 SB - IM MH - *DNA Methylation MH - *Genome-Wide Association Study MH - Sexual Maturation MH - Sleep/genetics MH - Circadian Rhythm/genetics PMC - PMC10464279 OTO - NOTNLM OT - Bedtime OT - DNA methylation OT - Epigenetics OT - Sleep initiation OT - Sleep latency COIS- The authors declare that they have no competing interests. EDAT- 2023/08/27 05:43 MHDA- 2023/08/28 06:42 PMCR- 2023/08/26 CRDT- 2023/08/26 23:25 PHST- 2023/01/19 00:00 [received] PHST- 2023/08/14 00:00 [accepted] PHST- 2023/08/28 06:42 [medline] PHST- 2023/08/27 05:43 [pubmed] PHST- 2023/08/26 23:25 [entrez] PHST- 2023/08/26 00:00 [pmc-release] AID - 10.1186/s13148-023-01553-2 [pii] AID - 1553 [pii] AID - 10.1186/s13148-023-01553-2 [doi] PST - epublish SO - Clin Epigenetics. 2023 Aug 26;15(1):136. doi: 10.1186/s13148-023-01553-2.