Genetic determination of sleep EEG profiles in healthy humans

Abstract

The contribution of slow brain oscillations including delta, theta, alpha, and sigma frequencies to the sleep electroencephalography (EEG) is finely regulated by circadian and homeostatic influences, and reflects functional aspects of wakefulness and sleep. Accumulating evidence demonstrates that individual sleep EEG patterns in non-rapid-eye-movement (NREM) sleep and rapid-eye-movement (REM) sleep are heritable traits. More specifically, multiple recordings in the same individuals, as well as studies in monozygotic and dizygotic twins suggest that a very high percentage of the robust interindividual variation and the high intraindividual stability of sleep EEG profiles can be explained by genetic factors (> 90% in distinct frequency bands). Still little is known about which genes contribute to different sleep EEG phenotypes in healthy humans. The genetic variations that have been identified to date include functional polymorphisms of the clock gene PER3 and of genes contributing to signal transduction pathways involving adenosine (ADA, ADORA2A), brain-derived neurotrophic factor (BDNF), dopamine (COMT), and prion protein (PRNP). Some of these polymorphisms profoundly modulate sleep EEG profiles; their effects are reviewed here. It is concluded that the search for genetic contributions to slow sleep EEG oscillations constitutes a promising avenue to identify molecular mechanisms underlying sleep-wake regulation in humans.

About Sleep's Role in Memory

“…Human sleep and particularly oscillatory EEG activity during sleep is highly heritable and very stable within individuals (689). In addition, large interindividual differences in the sleep EEG exist, which are more than 10 times higher than those, observed within subjects across multiple nights of sleep.…”

Reduced Sleep Spindles in Schizophrenia: A Treatable Endophenotype That Links Risk Genes to Impaired Cognition?

“…Despite this, little is known about the genetic underpinnings of sleep spindles. Genome-wide association studies (GWAS) have been conducted for sleep disorders (132), sleep duration (133) and insomnia (134), but genetic studies of the sleep EEG used relatively small samples and only a few candidate genes (135). To understand genetic contributions to spindle deficits in SZ, it is important to conduct well-powered genetic studies of spindles in humans.…”

Neuroimaging, cognition, light and circadian rhythms

“…The mechanisms underlying this hourglass-like process are still debated, but animal research suggests that it arises from a use-dependent local augmentation of sleep-promoting substances (adenosine (Basheer et al, 2004) and cytokines (Krueger, 2008)), from an increase in extracellular glutamate level (Dash et al, 2009), and/or from an experience-dependent increase of average brain synaptic strength, excitability and size during wakefulness (Vyazovskiy et al, 2008; Bushey et al, 2011). Other molecular markers of sleep loss have been identified in rodents (Franken and Dijk, 2009), while human polymorphisms have been associated with difference in sleep regulation [e.g., PERIOD3 (PER3) (Viola et al, 2007) , Adenosine Deaminase (ADA) , Adenosin A2a receptor (ADORA2A), Brain Derived Neurotrophic Factor (BDNF), Catechol-O-Methyltransferase (COMT) , human leukocyte antigen (HLA) , (Goel and Dinges, 2011), dopamine transporter (DA) , (Valomon et al, 2014), ABCC9 (Allebrandt et al, 2013); for review see (Landolt, 2011)]. At the macroscopic scale, the electroencephalogram (EEG) provides the best established markers of sleep need and intensity: slow wave activity (SWA; 0.5–4 Hz) during Non-Rapid Eye Movement (NREM) sleep (Dijk et al, 1987, 1997), and theta activity (4–8 Hz) during wakefulness (Cajochen et al, 2002).…”