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Exploring the Genetics of Sleep

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Article

Exploring the Genetics of Sleep

Credit: Pixabay
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The alarm is set for the morning, your head touches the pillow, and the events of the day become a distant memory as you sink into a state of relaxation and, eventually, sleep. Ironically, as you lay and physically do nothing for on average eight hours per night, your body is extremely awake, conducting a series of biological processes that aim to restore and rejuvenate, repair tissue, synthesize hormones and grow muscle. 

The National Sleep Foundation advises 7-9 hours of sleep per night for adults, 11-14 hours for young children, and between 8 and 10 hours for teenagers. Sleep is integral for cognitive processes such as processing and storing memories and contributing to positive mental health; the Dalai Lama himself claims that “sleep is the best meditation”. It’s of great concern, therefore, that 35.3% adults report having less than 7 hours of sleep during a typical 24-hour period. Ironically, despite spending an average 25 years of our lifetime asleep, our knowledge of why we sleep, and the purpose of sleep, is surprisingly limited. Increasing research is exploring the genetic and molecular forces driving the need for sleep and the effects of poor sleep, with some interesting findings that may have clinical implications. 

Genetic influences on sleep duration


Sleep duration varies greatly between individuals. Sometimes this is by choice - trading an extra hour of sleep to watch one more episode of Netflix or finishing the chapter of a book before dozing off is a common bedtime routine for many. However, for some individuals, getting to sleep can be a complete chore. Why is this, and how are our genes involved? 

The National Heart, Lung, and Blood Institute (NHLBI) conducted a study to investigate differences in a group of genes that may explain why some people require a lot more sleep, and others less.1 The scientists bred 13 generations of fruit flies that were either long sleepers, sleeping 18 hours per day, or short sleepers, sleeping three hours per day. When comparing genetic data between the two sets of flies, the scientists identified 126 differences in 80 genes that appeared to be associated with the duration of sleep. The genes that differed across the two populations have roles in several classic developmental and signalling pathways, including EGFR, Hippo, MAPK and Wnt to name a few. This work added further evidence for the suggested role of the Wnt signalling pathways in sleep; a previous epigenetic study demonstrated an alteration in the DNA methylation profile of molecules within the Wnt pathway in sleep deprived human subjects.2 

In the largest of its kind to date, Massachusetts General Hospital researchers conducted a genome wide association (GWAS) study in 446,000 people to identify genes related to sleep duration. The participants self-reported the amount of sleep they typically receive and provided DNA samples.  Published in Nature Communications, the findings revealed 76 novel gene regions associated with sleep duration.3 Co-senior and corresponding author Richa Saxena says “while follow-up studies are required to clarify the functional impact of these variants, the associated genes are known to play a role in brain development and in the transmission of signals between neurons”. Carrying just one genetic variant influenced sleep duration by one minute; however, carrying a greater number of variants was found to translate to up to an additional 22 extra minutes of sleep on average per night.

Short sleep duration was also found to be genetically associated with traits such as smoking and insomnia, whereas long-duration variants were linked with schizophrenia, coronary artery disease and type 2 diabetes. Co-lead author Samuel Jones, adds “as part of a wider body of work, our discoveries have the potential to aid the discovery of new treatments for sleep and sleep-related disorders.”

Sleeping is healing


When illness strikes, a visit to the doctors typically results in a prescription for plenty of bed rest and a good night’s sleep, but why? A recent study identified a single gene, the NEMURI gene that increases the need for sleep in a fruit fly model. Published in Science, the study shows that the protein encoded by NEMURI, an antimicrobial peptide (AMP), is secreted by brain cells in order to drive deep and prolonged sleep post infection.4 

By knocking out the NEMURI gene, the researchers were able to study precisely how it controls the flies’ sleep patterns. Their findings revealed that the flies were more easily aroused during daily sleep, and that their acute need for an increase in sleep (induced by sleep deprivation or infection) was reduced.  Of their results, Amita Sehgal, senior author of the publication, says “while it's a common notion that sleep and healing are tightly related, our study directly links sleep to the immune system and provides a potential explanation for how sleep increases during sickness.”

In contrast, when inducing overexpression of NEMURI, increased sleep and survival in bacteria-infected flies was observed when compared to healthy control flies. The fact that increased sleep during sickness promotes survival in the fly model suggests that the sleep-promoting role of the NEMURI protein may be of equal importance as its antimicrobial function.

The use of the Drosophila fruit fly model in sleep research is an increasing phenomenon, based on evidence that several characteristics of mammalian sleep biology are preserved in this type of fly. Of their study, Sehgal comments “as far as we know, humans do not have the molecule we report here, NEMURI.  However, they have similar kinds of molecules—anti-microbial peptides (AMPs).  Future research could examine whether AMPs affects sleep in mammalian models e.g. mice, which may be indicative of similar functions in humans.”

Sleeping isn’t cheating, and lack of sleep may cause DNA damage


We all know from experience that lack of sleep adversely affects our well being. Failing to get the optimal 7 hours of snooze can leave you feeling groggy, unproductive and in some occasions, physically unwell. At the most basic level of our being, our DNA, what is the impact of poor sleep? Despite the common motto that “sleeping is cheating”, the reality is that not getting enough sleep can have a negative impact on our DNA. A subgroup of the population that know sleep deprivation well are medical professionals. In an observational study published in Anaesthesia, researchers analyzed the impact of night shifts in 49 healthy full-time doctors. Baseline blood was collected from each doctor after three consecutive days of adequate sleep.5 24 participants were then required to work overnight on-site and had an additional blood sample taken on a morning after acute sleep deprivation.

Alarmingly, the results found that overnight on-site call participants had lower baseline DNA repair gene expression and an increased number of DNA breaks compared to those who had not completed a night shift. The authors note that larger prospective studies looking at the relationship between DNA damage, sleep, and chronic disease are warranted on the back of this research.

10 tips on how to fall asleep fast


Are you tossing and turning at night? Has getting to sleep become a chore for you? If so, read our infographic to learn 10 expert tips on how to fall asleep. 

References: 


1. Harbison, S., Serrano Negron, Y., Hansen, N. and Lobell, A. (2017). Selection for long and short sleep duration in Drosophila melanogaster reveals the complex genetic network underlying natural variation in sleep. PLOS Genetics, 13(12), p.e1007098.

2. Nilsson, E., Boström, A., Mwinyi, J. and Schiöth, H. (2016). Epigenomics of Total Acute Sleep Deprivation in Relation to Genome-Wide DNA Methylation Profiles and RNA Expression. OMICS: A Journal of Integrative Biology, 20(6), pp.334-342.

3. Dashti, H., Jones, S., Wood, A., Lane, J., van Hees, V., Wang, H., Rhodes, J., Song, Y., Patel, K., Anderson, S., Beaumont, R., Bechtold, D., Bowden, J., Cade, B., Garaulet, M., Kyle, S., Little, M., Loudon, A., Luik, A., Scheer, F., Spiegelhalder, K., Tyrrell, J., Gottlieb, D., Tiemeier, H., Ray, D., Purcell, S., Frayling, T., Redline, S., Lawlor, D., Rutter, M., Weedon, M. and Saxena, R. (2019). Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates. Nature Communications, 10(1).

4. Toda, H., Williams, J., Gulledge, M. and Sehgal, A. (2019). A sleep-inducing gene, nemuri, links sleep and immune function in Drosophila. Science, 363(6426), pp.509-515. 

5. Cheung, V., Yuen, V., Wong, G. and Choi, S. (2018). The effect of sleep deprivation and disruption on DNA damage and health of doctors. Anaesthesia, 74(4), pp.434-440.

Meet The Author
Molly Campbell
Molly Campbell
Science Writer
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