PAX8/PAX8-AS1 DNA Methylation Levels Are Associated with Objective Sleep Duration in Persons with Unexplained Hypersomnolence Using a Deep Phenotyping Approach

Details

• Personal Author:
  Alisch RS ; Cook JD ; Madrid A ; Papale LA ; Plante DT ; Prairie ML
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Behavior Genetics Nucleotides Occupational Health Safety Sleep Sleep Initiation And Maintenance Disorders
• Keywords:
  Author Keywords: Hypersomnolence Behavior Patterns DNA Methylation Gene Expression Genes Hypersomnia PAX8 PAX8-AS1 Polysomnography Psychomotor Function Sleep Sleep Disorders Sleepiness

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• ISSN:
  0161-8105
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Illinois ; Minnesota ; OSHA Region 5 ; Wisconsin
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  44
• Issue:
  10
• NIOSHTIC Number:
  nn:20063940
• Citation:
  Sleep 2021 Oct; 44(10):zsab108
• Contact Point Address:
  Reid S. Alisch, Department of Neurological Surgery, University Wisconsin - Madison, 600 Highland Avenue, Madison, WI 53792
• Email:
  alisch@wisc.edu
• Federal Fiscal Year:
  2022
• Performing Organization:
  University of Illinois at Chicago
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Sleep
• End Date:
  20290630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6b7cac94d63f5eb9d02da6457ea8c717b2184cc3816f7e3f3376814394785d507d1e729f24b3fc4d609924016359963c932ddf0d1acc2a668dfc83b1f9ee0952
• Download URL:
  https://stacks.cdc.gov/view/cdc/222473/cdc_222473_DS1.pdf
• File Type:
  [PDF - 1.19 MB ]