title: Transcriptional Signatures of Sleep Duration Discordance in Monozygotic Twins.
abstract: Habitual short sleep duration is associated with adverse metabolic, cardiovascular, and inflammatory effects. Co-twin study methodologies account for familial (eg, genetics and shared environmental) confounding, allowing assessment of subtle environmental effects, such as the effect of habitual short sleep duration on gene expression. Therefore, we investigated gene expression in monozygotic twins discordant for actigraphically phenotyped habitual sleep duration.
  
  
  
  Eleven healthy monozygotic twin pairs (82% female; mean age 42.7 years; SD = 18.1), selected based on subjective sleep duration discordance, were objectively phenotyped for habitual sleep duration with 2 weeks of wrist actigraphy. Peripheral blood leukocyte (PBL) RNA from fasting blood samples was obtained on the final day of actigraphic measurement and hybridized to Illumina humanHT-12 microarrays. Differential gene expression was determined between paired samples and mapped to functional categories using Gene Ontology. Finally, a more comprehensive gene set enrichment analysis was performed based on the entire PBL transcriptome.
  
  
  
  The mean 24-hour sleep duration of the total sample was 439.2 minutes (SD = 46.8 minutes; range 325.4-521.6 minutes). Mean within-pair sleep duration difference per 24 hours was 64.4 minutes (SD = 21.2; range 45.9-114.6 minutes). The twin cohort displayed distinctive pathway enrichment based on sleep duration differences. Habitual short sleep was associated with up-regulation of genes involved in transcription, ribosome, translation, and oxidative phosphorylation. Unexpectedly, genes down-regulated in short sleep twins were highly enriched in immuno-inflammatory pathways such as interleukin signaling and leukocyte activation, as well as developmental programs, coagulation cascade, and cell adhesion.
  
  
  
  Objectively assessed habitual sleep duration in monozygotic twin pairs appears to be associated with distinct patterns of differential gene expression and pathway enrichment. By accounting for familial confounding and measuring real life sleep duration, our study shows the transcriptomic effects of habitual short sleep on dysregulated immune response and provides a potential link between sleep deprivation and adverse metabolic, cardiovascular, and inflammatory outcomes.
authors.affiliation: Department of Neurology, University of Washington, Seattle, WA.|UW Medicine Sleep Center, University of Washington, Seattle, WA.|Washington State Twin Registry, Seattle, WA.|Center for Research in the Management of Sleep Disorders, University of Washington, Seattle, WA.
authors.forename: N F
authors.initials: NF
authors.lastname: Watson
authors.affiliation: Washington State Twin Registry, Seattle, WA.|Initiative for Research and Education to Advance Community Health, Elson S Floyd College of Medicine, Spokane, WA.
authors.forename: D
authors.initials: D
authors.lastname: Buchwald
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Delrow
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA.
authors.forename: W A
authors.initials: WA
authors.lastname: Altemeier
authors.affiliation: Center for Research in the Management of Sleep Disorders, University of Washington, Seattle, WA.|Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA.
authors.forename: M V
authors.initials: MV
authors.lastname: Vitiello
authors.affiliation: Division of Sleep Medicine/Department of Medicine and Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: A I
authors.initials: AI
authors.lastname: Pack
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA.
authors.forename: M
authors.initials: M
authors.lastname: Bamshad
authors.affiliation: Initiative for Research and Education to Advance Community Health, Elson S Floyd College of Medicine, Spokane, WA.
authors.forename: C
authors.initials: C
authors.lastname: Noonan
authors.affiliation: UW Medicine Sleep Center, University of Washington, Seattle, WA.|Department of Medicine, University of Washington, Seattle, WA.
authors.forename: S A
authors.initials: SA
authors.lastname: Gharib
mesh_terms: D056044:Actigraphy; D000328:Adult; D004777:Environment; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007109:Immunity / Q000235:genetics; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D010085:Oxidative Phosphorylation; D010641:Phenotype; D012890:Sleep / Q000235:genetics* / Q000502:physiology*; D013997:Time Factors; D059467:Transcriptome / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*; D015854:Up-Regulation
keywords: Gene expression; Leukocyte.; Monozygotic; Sleep duration; Twins