title: PER3 polymorphism predicts sleep structure and waking performance.
abstract: Circadian rhythmicity and sleep homeostasis interact to regulate sleep-wake cycles [1-4], but the genetic basis of individual differences in sleep-wake regulation remains largely unknown [5]. PERIOD genes are thought to contribute to individual differences in sleep timing by affecting circadian rhythmicity [6], but not sleep homeostasis [7, 8]. We quantified the contribution of a variable-number tandem-repeat polymorphism in the coding region of the circadian clock gene PERIOD3 (PER3) [9, 10] to sleep-wake regulation in a prospective study, in which 24 healthy participants were selected only on the basis of their PER3 genotype. Homozygosity for the longer allele (PER3(5/5)) had a considerable effect on sleep structure, including several markers of sleep homeostasis: slow-wave sleep (SWS) and electroencephalogram (EEG) slow-wave activity in non-rapid eye movement (non-REM) sleep and theta and alpha activity during wakefulness and REM sleep were all increased in PER3(5/5) compared to PER3(4/4) individuals. In addition, the decrement of cognitive performance in response to sleep loss was significantly greater in the PER3(5/5) individuals. By contrast, the circadian rhythms of melatonin, cortisol, and peripheral PER3 mRNA expression were not affected. The data show that this polymorphism in PER3 predicts individual differences in the sleep-loss-induced decrement in performance and that this differential susceptibility may be mediated by its effects on sleep homeostasis.
authors.affiliation: Surrey Sleep Research Centre, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, UK.
authors.forename: Antoine U
authors.initials: AU
authors.lastname: Viola
authors.forename: Simon N
authors.initials: SN
authors.lastname: Archer
authors.forename: Lynette M
authors.initials: LM
authors.lastname: James
authors.forename: John A
authors.initials: JA
authors.lastname: Groeger
authors.forename: June C Y
authors.initials: JC
authors.lastname: Lo
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Skene
authors.forename: Malcolm
authors.initials: M
authors.lastname: von Schantz
authors.forename: Derk-Jan
authors.initials: DJ
authors.lastname: Dijk
mesh_terms: D000328:Adult; D002940:Circadian Rhythm; D004569:Electroencephalography; D005260:Female; D006706:Homeostasis; D006720:Homozygote; D006801:Humans; D008297:Male; D018598:Minisatellite Repeats; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012333:RNA, Messenger; D012890:Sleep / Q000235:genetics; D012892:Sleep Deprivation / Q000235:genetics / Q000503:physiopathology; D012895:Sleep, REM / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014851:Wakefulness / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; C512644:PER3 protein, human; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D014157:Transcription Factors