LAUSR

The biological basis of daytime sleepiness and excessive sleep duration in patients with unexplained hypersomnolence is unknown. However, a growing body of evidence suggests modulations in the epigenome coincide with objective measures of sleep, suggesting epigenetic mechanisms may be related to hypersomnolence. Previously, we identified significant correlations between saliva DNA methylation abundance at nine CpG sites located in the PAX8/PAX8-AS1 genes and total sleep time measured using polysomnography in unmedicated, clinical patients with unexplained hypersomnolence. Since psychotropic medications frequently affect clinical sleep testing and may also affect DNA methylation, here we attempted to replicate prior findings in a separate, medicated sample. Forty-three medicated clinical patients with unexplained hypersomnolence were drawn from a larger study of a multimodal sleep assessment that included ad libitum overnight polysomnography. Pyrosequencing quantified DNA methylation at the previously identified CpG sites in PAX8/PAX8-AS1. Multivariate linear models, adjusting for age, sex, and body mass index (BMI), assessed relationships between total sleep time and DNA methylation at these prespecified CpG sites. Participants were young -to middle-aged (Mean Age = 32.2±10 years) and predominantly female (Percent Female = 95.3%), with a mean BMI of 27.8±5.4kg/m2. Epworth Sleepiness Scale (ESS) score was consistent with complaints of daytime sleepiness (Mean ESS =15.1±-4.3). Total sleep time on ad libitum polysomnography was 9.2±1.7 hours (range 5.6-12.8 hours). No significant associations between DNA methylation at the PAX8/PAX8-AS1 CpG sites and sleep duration were identified in adjusted models. We were unable to replicate findings of an association between sleep duration and DNA methylation levels at specific PAX8/PAX8-AS1 CpG sites in medicated patients with unexplained hypersomnolence. Further research to clarify whether this is a result of medications affecting the DNA methylation levels at these CpG sites or previously identified associations between DNA methylation of PAX8/PAX8-AS1 and sleep length are spurious will require replication of prior findings in a novel unmedicated cohort and quantification of within-subjects effects of psychotropic medications on DNA methylation levels in genes of interest. AASM Foundation (229 SR-20 - Diversity Supplement Grant)