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PAX8/PAX8-AS1 DNA methylation levels are associated with objective sleep duration in persons with unexplained hypersomnolence using a deep phenotyping approach.
Plante, David T; Papale, Ligia A; Madrid, Andy; Cook, Jesse D; Prairie, Michael L; Alisch, Reid S.
Afiliación
  • Plante DT; Department of Psychiatry, Madison, WI.
  • Papale LA; Department of Neurological Surgery, Madison, WI.
  • Madrid A; Department of Neurological Surgery, Madison, WI.
  • Cook JD; Neuroscience Training Program, University of Wisconsin - Madison, Madison, WI.
  • Prairie ML; Department of Psychology, Madison, WI.
  • Alisch RS; University of Minnesota School of Medicine, Minneapolis, MN.
Sleep ; 44(10)2021 10 11.
Article en En | MEDLINE | ID: mdl-34145460
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilación de ADN / ARN Largo no Codificante / Factor de Transcripción PAX8 / Trastornos de Somnolencia Excesiva Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Sleep Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilación de ADN / ARN Largo no Codificante / Factor de Transcripción PAX8 / Trastornos de Somnolencia Excesiva Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Sleep Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos