Circadian gene variants influence sleep and the sleep electroencephalogram in humans

Apr 19, 2016Chronobiology international

Circadian gene differences are linked to sleep patterns and brain activity during sleep in humans

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Abstract

A common variant in the Period2 gene is associated with 20 minutes less slow-wave sleep in carriers compared to noncarriers.

The variant in Period2 (PER2) is linked to a 22% reduction in slow-wave sleep duration.
Spectral analysis indicated that the PER2 polymorphism correlates with reduced EEG power density in the low delta range during non-REM sleep.
Lower slow-wave activity was observed in the early part of the sleep episode among carriers of the PER2 variant.
A rare variant in Melatonin Receptor 1B is associated with an average of 65 minutes longer latency to REM sleep in minor allele carriers.
These findings suggest that circadian-related genes may influence aspects of sleep architecture and the sleep EEG.

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The sleep electroencephalogram (EEG) is highly heritable in humans and yet little is known about the genetic basis of inter-individual differences in sleep architecture. The aim of this study was to identify associations between candidate circadian gene variants and the polysomnogram, recorded under highly controlled laboratory conditions during a baseline, overnight, 8 h sleep opportunity. A candidate gene approach was employed to analyze single-nucleotide polymorphisms from five circadian-related genes in a two-phase analysis of 84 healthy young adults (28 F; 23.21 ± 2.97 years) of European ancestry. A common variant in Period2 (PER2) was associated with 20 min less slow-wave sleep (SWS) in carriers of the minor allele than in noncarriers, representing a 22% reduction in SWS duration. Moreover, spectral analysis in a subset of participants (n = 37) showed the same PER2 polymorphism was associated with reduced EEG power density in the low delta range (0.25-1.0 Hz) during non-REM sleep and lower slow-wave activity (0.75-4.5 Hz) in the early part of the sleep episode. These results indicate the involvement of PER2 in the homeostatic process of sleep. Additionally, a rare variant in Melatonin Receptor 1B was associated with longer REM sleep latency, with minor allele carriers exhibiting an average of 65 min (87%) longer latency from sleep onset to REM sleep, compared to noncarriers. These findings suggest that circadian-related genes can modulate sleep architecture and the sleep EEG, including specific parameters previously implicated in the homeostatic regulation of sleep.

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Circadian gene variants influence sleep and the sleep electroencephalogram in humans

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