PER3 polymorphism predicts sleep structure and waking performance

Curr Biol. 2007 Apr 3;17(7):613-8. doi: 10.1016/j.cub.2007.01.073. Epub 2007 Mar 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Circadian Rhythm
  • Electroencephalography
  • Female
  • Homeostasis
  • Homozygote
  • Humans
  • Male
  • Minisatellite Repeats
  • Nuclear Proteins / genetics*
  • Period Circadian Proteins
  • Polymorphism, Genetic*
  • Prospective Studies
  • RNA, Messenger
  • Sleep Deprivation / genetics
  • Sleep Deprivation / physiopathology
  • Sleep* / genetics
  • Sleep, REM / genetics
  • Transcription Factors / genetics*
  • Wakefulness* / genetics


  • Nuclear Proteins
  • PER3 protein, human
  • Period Circadian Proteins
  • RNA, Messenger
  • Transcription Factors