PAX8/PAX8-AS1 DNA methylation levels are associated with objective sleep duration in persons with unexplained hypersomnolence using a deep phenotyping approach. Issue 10 (18th June 2021)

• Record Type: Journal Article
• Authors: Plante, David T; Papale, Ligia A; Madrid, Andy; Cook, Jesse D; Prairie, Michael L; Alisch, Reid S
• Is Part Of: Sleep. Volume 44:Issue 10(2021)
• Publication Date: 2021-06-18
• Subjects: hypersomnolence -- PAX8 -- PAX8-AS1 -- DNA methylation -- polysomnography -- sleepiness -- hypersomnia -- sleep; Sleep -- Physiological aspects -- Periodicals; Sleep disorders -- Periodicals; Sommeil -- Aspect physiologique -- Périodiques; Sommeil, Troubles du -- Périodiques; Sleep disorders; Sleep -- Physiological aspects; Sleep -- physiological aspects; Sleep Wake Disorders; Psychophysiology; Electronic journals; Periodicals; 616.8498
• DOI: 10.1093/sleep/zsab108
• Languages: English
• ISSNs: 0161-8105

Abstract

Abstract: Study Objectives: Patients with unexplained hypersomnolence have significant impairment related to daytime sleepiness and excessive sleep duration, the biological bases of which are poorly understood. This investigation sought to examine relationships between objectively measured hypersomnolence phenotypes and epigenetic modification of candidate hypersomnolence genes to advance this line of inquiry. Methods: Twenty-eight unmedicated clinical patients with unexplained hypersomnolence were evaluated using overnight ad libitum polysomnography, multiple sleep latency testing, infrared pupillometry, and the psychomotor vigilance task. DNA methylation levels on CpG sites annotated to 11 a priori hypersomnolence candidate genes were assessed for statistical association with hypersomnolence measures using independent regression models with adjusted local index of significance (aLIS) P -value threshold of 0.05. Results: Nine CpG sites exhibited significant associations between DNA methylation levels and total sleep time measured using ad libitum polysomnography (aLIS p -value < .05). All nine differentially methylated CpG sites were annotated to the paired box 8 ( PAX8 ) gene and its related antisense gene ( PAX8-AS1 ). Among these nine differentially methylated positions was a cluster of five CpG sites located in the body of the PAX8 gene and promoter of PAX8-AS1 . Conclusions: This study demonstrates that PAX8/PAX8-AS1 DNA methylation levels are associated with total sleep time in persons with unexplained hypersomnolence. Given prior investigations that have implicated single nucleotide polymorphisms in PAX8/PAX8-AS1 with habitual sleep duration, further research that clarifies the role of DNA methylation levels on these genes in the phenotypic expression of total sleep time is warranted.