Current biology : CBMar 10, 2007

PER3 gene variation is linked to sleep patterns and daytime performance

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 25, 2026

Abstract

Homozygosity for the longer allele of the PERIOD3 gene (PER3(5/5)) is associated with increased slow-wave sleep and a greater cognitive performance decrement due to sleep loss.

The longer PER3 allele significantly affects sleep structure, enhancing slow-wave sleep and EEG slow-wave activity during non-REM sleep.
Increased theta and alpha activity during wakefulness and REM sleep is also observed in individuals with the PER3(5/5) genotype.
Cognitive performance decline in response to sleep loss is notably greater in those with the PER3(5/5) genotype.
Circadian rhythms of melatonin, cortisol, and peripheral PER3 mRNA expression remain unchanged regardless of PER3 genotype.
The findings suggest that this genetic variation may influence individual differences in sleep homeostasis and performance under sleep deprivation.

Simplified

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.

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PER3 gene variation is linked to sleep patterns and daytime performance

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