Mutations in Metabotropic Glutamate Receptor 1 Contribute to Natural Short Sleep Trait

Machine learning approaches to identify sleep genes

“…This approach successfully identifies key pathways that are involved in sleep regulation. In addition to our validation of the NF-κB pathway, a few of the top candidate genes, Mef2c 63 , GRM1 64 , and Tac1 65 were independently validated. Our study highlights the power of ML-based tools to integrate prior knowledge and genome-wide data to study genetic regulation of sleep and other complex behaviors.…”

Some Twist of Molecular Circuitry Fast Forwards Overnight Sleep Hours: A Systematic Review of Natural Short Sleepers' Genes

“…During sleep, synapses are loosened by Homer1a (sleep regulator) and mGluR1/mGluR5 via signaling of neuromodulators promoting sleep-wake cycles [53], as depicted in Figure 4. In another study [2], two rare independent mutations, K50230 and K07331, of the glutamate metabotropic receptor 1 gene (GRM1) had been identified in two unrelated FNSS families. K50230 altered the arginine into a tryptophan at position 889 in the C-terminal intracellular domain of the isoform GRM1b-R889W, and K07331 substituted the serine into an alanine at position 458 in the N-terminal extracellular domain yielding the isoform GRM1-S458A.…”

“…[1] One of the most frequently asked sleep questions would be the optimal sleep hours for most individuals or the minimum sleep requirement to thrive in their lives. Although the report from Sleep Foundation [www.sleepfoundation.org] says that the average United States (US) adult sleeps about 7.4 hours per day during their work-offs [1], it also states that the optimal sleep duration for most adults is eight hours each day to sustain their health in general [2]. Prolonged periods of short sleep hours either due to social needs or comorbid pathologic conditions will gradually deteriorate the quality of life as a whole.…”

“…However, it is a less popular concept that this term can be composed of two different phenomena of sleep: short sleep phenotype and deprived sleep. The former group is also classified as natural short sleepers (NSS) who usually sleep four to six hours a day without any negative impact on health or daytime drowsiness [2]; meanwhile, insufficient sleep is a pathologic condition needed to be managed and corrected. NSS is also not to be confused with the term familial advanced sleep phase (FASP), or advanced sleep phase (ASP), in which affected individual displays spontaneous early sleep onset and offset times while overall sleep duration is unaffected [4].…”

“…Other challenges of studying NSS include (i) screening of other sleep-wake variants with short sleep patterns related to the subject's underlying comorbid medical condition or pharmacological influence [6], (ii) reliability of subjective reports of short sleep patterns, which need to be confirmed by objective measurements conducted by wrist actimetry sensors and home EEG units to detect sleep/wake transition and quality of sleep [1], and (iii) recruitment difficulty due to undetected NSS cases due to subject's perception of own phenotypic short sleep behavior as non-problematic and dependence on research subject's interest in sleep research and active involvement [2]. While facing such limitations in human studies, many NSS phenotype research is based on animal studies compared to human sleep behaviors and gene sequencing.…”