Circadian gene variants influence sleep and the sleep electroencephalogram in humans |
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| Authors: | Anne-Marie Chang Andrew C. Bjonnes Daniel Aeschbach Orfeu M. Buxton Joshua J. Gooley Clare Anderson |
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| Affiliation: | 1. Division of Sleep and Circadian Disorders, Department of Medicine and Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA;2. Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA;3. Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA;4. Department of Biobehavioral Health, Pennsylvania State University, University Park, PA, USA;5. Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA;6. Department of Anesthesia, Critical Care and Pain Medicine and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA;7. Institute of Aerospace Medicine, German Aerospace Center, Cologne, Germany;8. Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA |
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| 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. |
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| Keywords: | Circadian genes sleep EEG slow-wave sleep slow-wave activity |
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