title: Blood-gene expression reveals reduced circadian rhythmicity in individuals resistant to sleep deprivation.
abstract: OBJECTIVE
  To address whether changes in gene expression in blood cells with sleep loss are different in individuals resistant and sensitive to sleep deprivation.
  
  
  METHODS
  Blood draws every 4 h during a 3-day study: 24-h normal baseline, 38 h of continuous wakefulness and subsequent recovery sleep, for a total of 19 time-points per subject, with every 2-h psychomotor vigilance task (PVT) assessment when awake.
  
  
  METHODS
  Sleep laboratory.
  
  
  METHODS
  Fourteen subjects who were previously identified as behaviorally resistant (n = 7) or sensitive (n = 7) to sleep deprivation by PVT.
  
  
  METHODS
  Thirty-eight hours of continuous wakefulness.
  
  
  RESULTS
  We found 4,481 unique genes with a significant 24-h diurnal rhythm during a normal sleep-wake cycle in blood (false discovery rate [FDR] < 5%). Biological pathways were enriched for biosynthetic processes during sleep. After accounting for circadian effects, two genes (SREBF1 and CPT1A, both involved in lipid metabolism) exhibited small, but significant, linear changes in expression with the duration of sleep deprivation (FDR < 5%). The main change with sleep deprivation was a reduction in the amplitude of the diurnal rhythm of expression of normally cycling probe sets. This reduction was noticeably higher in behaviorally resistant subjects than sensitive subjects, at any given P value. Furthermore, blood cell type enrichment analysis showed that the expression pattern difference between sensitive and resistant subjects is mainly found in cells of myeloid origin, such as monocytes.
  
  
  CONCLUSIONS
  Individual differences in behavioral effects of sleep deprivation are associated with differences in diurnal amplitude of gene expression for genes that show circadian rhythmicity.
authors.affiliation: Center for Sleep and Circadian Neurobiology and Division of Sleep Medicine/Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA and Department of Respiratory Medicine and Sleep, Landspitali - The National University Hospital, Iceland and Faculty of Medicine, University of Iceland, Iceland.
authors.forename: Erna S
authors.initials: ES
authors.lastname: Arnardottir
authors.affiliation: Department of Exploratory and Translational Sciences, Merck Research Laboratories, West Point, PA.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Nikonova
authors.affiliation: Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Shockley
authors.affiliation: Department of Exploratory and Translational Sciences, Merck Research Laboratories, West Point, PA.
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Podtelezhnikov
authors.affiliation: Faculty of Medicine, University of Iceland, Iceland.
authors.forename: Ron C
authors.initials: RC
authors.lastname: Anafi
authors.affiliation: Department of Exploratory and Translational Sciences, Merck Research Laboratories, West Point, PA.
authors.forename: Keith Q
authors.initials: KQ
authors.lastname: Tanis
authors.affiliation: Center for Sleep and Circadian Neurobiology and Division of Sleep Medicine/Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA and.
authors.forename: Greg
authors.initials: G
authors.lastname: Maislin
authors.affiliation: Department of Exploratory and Translational Sciences, Merck Research Laboratories, West Point, PA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Stone
authors.affiliation: Neuroscience Department, Merck Research Laboratories, West Point, PA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Renger
authors.affiliation: Neuroscience Department, Merck Research Laboratories, West Point, PA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Winrow
authors.affiliation: Center for Sleep and Circadian Neurobiology and Division of Sleep Medicine/Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Allan I
authors.initials: AI
authors.lastname: Pack
mesh_terms: D000328:Adult; D001288:Attention / Q000502:physiology; D015415:Biomarkers; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007206:Individuality; D008297:Male; D011597:Psychomotor Performance; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D013997:Time Factors; D014851:Wakefulness / Q000502:physiology
chemical_list: D015415:Biomarkers
keywords: circadian rhythm; gene expression; microarray analysis; psychomotor vigilance test; sleep deprivation