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Chronobiol Int. 2016;33(5):561-73. doi: 10.3109/07420528.2016.1167078. Epub 2016 Apr 18.

Circadian gene variants influence sleep and the sleep electroencephalogram in humans.

Chang AM1,2,3,4, Bjonnes AC3,5, Aeschbach D1,2,6, Buxton OM1,2,4,7, Gooley JJ1,2, Anderson C1,2, Van Reen E1,2, Cain SW1,2, Czeisler CA1,2, Duffy JF1,2, Lockley SW1,2, Shea SA1,2,8, Scheer FA1,2, Saxena R1,2,3,5.

Author information

1
a Division of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology , Brigham and Women's Hospital , Boston , MA , USA.
2
b Division of Sleep Medicine , Harvard Medical School , Boston , MA , USA.
3
c Medical and Population Genetics , Broad Institute of Harvard and Massachusetts Institute of Technology , Cambridge , MA , USA.
4
d Department of Biobehavioral Health , Pennsylvania State University , University Park , PA , USA.
5
e Department of Anesthesia, Critical Care and Pain Medicine and Center for Human Genetic Research , Massachusetts General Hospital , Boston , MA , USA.
6
f Institute of Aerospace Medicine , German Aerospace Center , Cologne , Germany.
7
g Department of Social and Behavioral Sciences , Harvard School of Public Health , Boston , MA , USA.
8
h Oregon Institute of Occupational Health Sciences , Oregon Health & Science University , Portland , OR , USA.

Abstract

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.

KEYWORDS:

Circadian genes; sleep EEG; slow-wave activity; slow-wave sleep

PMID:
27089043
PMCID:
PMC5267557
DOI:
10.3109/07420528.2016.1167078
[Indexed for MEDLINE]
Free PMC Article

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