Chronotypes: Sleep, Addiction, and More

In the modern age one will often be bombarded by health tabloids with snappy titles attempting to sell you on their new diet, supplement, or lifestyle when looking for health advice. They often expound a new diet that is proven by SCIENTISTS to be ideal for sleep, lifestyle, and weight loss(compared to the other ones that are also proven to be ideal by the ever-pervasive scientists). Among this buzz of marketing it can often be difficult to get any concrete info on what's best for oneself, which is why we need to look to genetics. 

Examples of some chronotype categories

Chronotypes are a term utilised by sleep scientists to categorise individuals based on inborne preferences related to their internal clock/circadian rhythms. This genetic predisposition can be positively correlated with a variety of interesting things that one may be believe are simply lifestyle-related. Things like preferring late nights or mornings for work, risk for video game or internet addiction, and even appetite have been positively correlated to chronotypes. Being more of a "neutral" chronotype, as in following the sun more or less, is correlated with less risk of obesity, normal metabolism, and less risk for addiction. On the contrary, a more "extreme" chronotype, those being extreme night owls or early risers, are more at risk for sleep-related illness, addiction, and potentially more. Overall, if one is concerned about their health it may be worth looking into chronotype studies to figure out how their genetics may be affecting their day to day. 

Sources: 

https://www.yahoo.com/lifestyle/best-time-wake-day-genetics-194209285.html?guccounter=1

https://www.sleepfoundation.org/how-sleep-works/chronotypes

https://www.sciencedirect.com/topics/psychology/chronotype#:~:text=Chronotype%20refers%20to%20the%20endogenous,to%20personality%20and%20lifestyle%20aspects.

Do your genes tell you if you're an early riser or a night owl?

  This article discusses a study performed by Dr.John Capra at the University of California. In his study, he looked at the link between Neanderthal DNA and people who like waking up early in the morning. Capra hypothesized that this is because the human population is said to have started in Africa. As migration took place and humans moved farther from the equator they began adapting to the changes in sunlight throughout time. Capra also found that this gene not only affects the time that people wake up but also their appetite and metabolism. Although this experiment doesn’t provide life-changing information for most, the article states that it brings us one step closer to understanding how Neanderthal DNA affects humans today. 

I found this article very interesting because I have never thought about my genes affecting my ability to wake up in the morning. I also noticed that the study was conducted using limited amounts of volunteers from only one part of the world. This could largely affect that data due to the lack of diversity in the study.  This could pose questions such as, do these genes affect some people more than others? And, as mentioned in the article does a person's geographical location affect a person's sleep schedule? I am interested to see what kind of discoveries this experiment leads to.

Poor Sleep Plus Genes Might Raise Some Folks' Asthma Risk

The article elaborated on the study, which emphasized the increasing chances of being diagnosed with the respiratory condition due to poor sleep quality and genetic inheritance linked to asthma. According to the report from the participants in the U.K., having a healthy sleep routine can lower the risk of being diagnosed with a respiratory condition. Sleep disorders, such as unfavorable sleep duration and insomnia, are associated with chronic inflammation, which can generate pro-inflammatory cytokines that result in cellular infiltration and airway inflammation, which may increase the risk of having asthma. Researchers studied how detecting and treating sleep disorders early on might lessen the risks, regardless of genetic predisposition. 

I thought that the article was on point in elaborating on the main study about the connection between sleeping habits and genetic inheritance and the risk of asthma. The survey that researchers used showed its credibility, especially when it explained how many people were diagnosed with respiratory conditions, and the results helped to determine the patterns that can be improved to help others prevent having higher risks for asthma. 

Sources: 

https://www.usnews.com/news/health-news/articles/2023-04-04/poor-sleep-plus-genes-might-raise-some-folks-asthma-risk 

https://www.precisionmedicineonline.com/microarrays-multiplexing/asthma-risk-heightened-genetic-predisposition-poor-sleep-patterns

You are Getting Sleepy: Tiredness, Proteins, and DNA Repair

 

Researchers in Israel have been working to unravel the mystery of sleep by examining the mechanisms that cause organisms to get tired. Homeostatic sleep pressure builds up in our body the longer we stay awake and begins to decrease as we fall asleep. But what causes homeostatic pressure to increase to the point of tiredness and how does sleep cause it decrease? The pressure is built during waking hours due to accumulating DNA damage in neurons, caused by things like UV light, neuronal activity, oxidative stress, radiation, and enzymatic errors. And during sleep, sleep recruit repair systems correct DNA breaks that cause excessive DNA damage in our brains. To see if DNA damage was the trigger for homeostatic pressure and sleep state, the researchers examined zebrafish. These fish are particularly easy to study because of their nocturnal sleeping patterns and simple brain that is comparable to a human's. 

Methods involving irradiation, pharmacology, and optogenetics were used to induce DNA damage in the zebrafish. They discovered that after subjecting the zebrafish to light interruption during the dark period when they'd be sleeping, six hours of sleep was enough to reduce DNA damage. But with less than six hours of sleep, DNA damage was not adequately reduced and the zebrafish continued to sleep during daylight hours. The mechanism that tells them (and us) to sleep is the protein PARP1. It's the among the first to rapidly respond to DNA damage sites in cells and recruits relevant systems to clean out the damage. PARP1 increasingly clusters at DNA break sites during wakefulness and decreases during sleep. Inhibition of the protein in zebrafish meant that the fish weren't aware they were tired, didn't sleep, and the DNA didn't get repaired. Understanding the purpose of sleep on a cellular level may help with future research on sleep disturbances, aging, and neurogenerative disorders. 

https://www.sciencedaily.com/releases/2021/11/211118203657.htm

Insomnia Genetically Tied to Increased Risk of Aneurysm

A new study of 70,000 adults revealed that those who are genetically predisposed to insomnia have an increased risk of brain bleeds, more commonly known as aneurysms. Those who have genetic insomnia are 24% more likely to experience aneurysms, which are usually fatal within 24 hours. 

This study centered around lifestyle choices, but also focused on the IL6R gene, which is responsible for the interleukin‐6 receptor (IL6R). Disruptions or mutations in this gene are associated with chronic insomnia. This gene also enables exposure to other genetic diseases such as multiple myeloma, autoimmune diseases, and prostate cancer.

In general, any sleeping disorder leads to higher blood pressure, so doing research to try to solve the root cause of these sleeping disorders will greatly help lower the rate of aneurysms. However, it is unclear that this specific gene is the only genetic factor responsible for an increased risk of aneurysms.

The Genes Associated with the Functions Found in the Hypothalamus

A recent study has been able to identify the genes involved with various functions from the hypothalamus. In the news article “Researchers Use Model of Hypothalamus to Implicate Genes Associated with Sleep, BMI, Puberty, and More,” a research study was conducted by the Children’s Hospital of Philadelphia to determine the genes that are responsible for functions like sleep, BMI, and puberty within the brain. The hypothalamus is located in the center of the brain and is part of the limbic system. It is responsible for releasing hormones throughout the body, body temperature, reproduction, sleep, hunger, thirst, etc. Since it is located in the middle of the brain it can be difficult to  study the genes that work to provide proper function to the body. In order to find these specific genes, a model had to be used to be able to further examine the different components of the hypothalamus. 

The research team used an embryonic stem cell model to investigate the gene expression in the hypothalamus. It provided them with the information on the genes before the hypothalamus has developed and even afterwards. The team was able to discover that the gene BDNF is responsible for body mass index while the gene PER2 is involved with sleep regulation. This particular research will help us understand the many functions of the hypothalamus but also the abnormalities that can occur within this part of the brain. 

https://www.chop.edu/news/researchers-use-model-hypothalamus-implicate-genes-associated-sleep-bmi-puberty-and-more 

https://www.webmd.com/brain/what-to-know-about-hypothalamus 

The Genetic Roots of Sleep Issues and Autism May Be Related

According to a new study of autistic people and their relatives, the genetic factors that have a role in autism may be entwined with those that underlie insomnia. This discovery may be able to help explain the common co-occurrence of autism and sleep issues. According to previous research, up to 90 percent of people with autism encounter disrupted sleep, and approximately 30 percent have a clinical diagnosis of a certain sleep disorder. The study reveals that close relatives of those with autism are also at a high risk to develop insomnia.

50,097 autistic people, along with nearly 56,000 of their full siblings, 31,669 half-siblings and 214,665 cousins were identified by using the Swedish national health registries. Approximately 23 percent of the autistic participants suffered from insomnia or took melatonin, in comparison with 1.1 percent of the control group participants. The study showed that the more closely related the relatives are to the austistic individual, the higher the chances that they will suffer from sleeping issues. For example, identical twins had about 6.6 times the typical odds of suffering from insomnia, while cousins had approximately 1.3 times the usual odds. Out of this study, shared genetic factors explained 94 percent of the correlation, whilst nonshared environmental influences accounted for only 6 percent.

Helpful Links:

Study: Etiological links between autism and difficulties in initiating and maintaining sleep: a familial co-aggregation and twin study

Article: Genetic roots of sleep issues, autism may be entwined

How Much Sleep Do You Need Every Night?

Do you feel well rested with more or less sleep? According to this New York Times article you may have a gene causing you to sleep less than the average amount of hours adults need but still feel refreshed and ready for the day. Brad Johnson serves as his own alarm clock and can never seem to sleep more than six hours a day. Johnson and several family members also share this same characteristic. Dr. Louis Ptacek and his colleagues collected the DNA of Johnson and these family members and found the same mutation in each family member. They then put that same mutation into mice and compared them to regular mice. The mice with the mutation needed one less hour of sleep than the unaffected mice. This gene is called ADRB1, which causes a “heightened wakefulness and impacts wakeful regulation.” I think this study is really interesting because I never asked myself why humans need to sleep and how we know to wake up. It’s crazy that one small mutation can regulate the amount of time someone sleeps to fully function throughout the day.

Discovering the Genes Behind Sleep

 Scientists have been trying to uncover the mechanism and purpose of sleep for decades. We know that all animals must sleep to survive and that there is a circadian rhythm which prepares the body for rest. What we do not yet know is how the body determines how much sleep it needs. Three genes have recently been identified as being related to sleep. These genes were identified by looking for matching mutations within a family who's sleep cycle is set 4 hours ahead of most of the population.

While these three genes do not change much on their own, this is a step towards improving our health. Currently the only measure of whether or not you are getting enough sleep is how sleepy you feel. The hope is that after all sleep genes have been identified, we will have a more quantifiable answer to that question. After studying the sleep genes, scientists will be able to determine how much sleep you need, what is a disorder vs what is habit, and when your body is best able to go to sleep. Some people feel well rested with less sleep than others, seemingly reducing the harmful effects of deprivation. Understanding the genes that cause this may open the way to for medication that helps people feel well rested.

As someone who has never been able to get sound sleep at a reasonable hour, I would like to know if it is because of lifestyle choices or a genetic predisposition. I hope this project gets completed quickly and accomplishes everything it set out to because I, and almost half of all Americans, do not get enough sleep.



Links:
https://www.nytimes.com/2019/11/19/magazine/will-science-ever-give-us-a-better-nights-sleep.html?searchResultPosition=3
https://www.sciencemag.org/news/2019/08/genetic-mutation-makes-people-feel-rested-just-6-hours-sleep

Hibernating Bears and their Gene Expression

                The average black bear hibernates for 5-7 months, depending on their location. During this period, many physiological changes occur within the animal's body. Their body temperatures lower, they stop producing waste, metabolic rates severely decline and they even stop eating for these long periods. In order to prepare for this hibernation period, bears will eat upwards of 20,000 calories a day in the summer months, adding around 4-5 inches of fat for insulation under their coat. By the time the hibernation period is over, they will have lost almost 20% of their body fat, and again be ravenously hungry. While it is still being studied whether or not these changes come from environmental factors, like scarcity of food, or if they come from different hormones being released, it is evident that bears express different genes during winter hibernation, and the summer active periods.

              In a recent study of the America Black Bear, 245 genes in the heart, and 319 genes in the liver identified to be expressed differently during the summer and winter months. Of these a select 24 genes had significantly elevated expression. It was found that these genes mainly were involved in the lipid catabolism, and protein synthesis. During hibernation, these processes are linked to important things like keeping muscles from experiencing atrophy, and keeping the heart strong as the animals slows down its metabolic processes. A bear in hibernation will severely slow down it's heart rate. These different gene expressions can help keep the bear's heart strong, and at the same time allow the bear to walk when it is time to come out of the den. After all, wouldn't it be hard to stand up after taking a nap for 6 months? The expression of these genes help contribute to the muscle preservation of the bear. 

          As the bear sleeps through the winter, another phenomena occurs, thanks to genes being expressed differently. At the mRNA and protein level, a slow shift from glucose catabolism to glucose synthesis occurs in the liver. This allows the bear to have energy, which will be used to power the brain and other tissue that is being starved.  While the bears hibernate and slowly stop breaking down glucose for cellular respiration, they are able to reduce their metabolic rate by nearly 50%. 

          

        I have always love animals, but bears are truly incredible, and have always interested me. It is a wonder that they can accomplish the feat of going months and months on end without eating or defecating. I first started looking into this topic about a year ago, and have been interested ever since. There are a few researchers who say that bears never actually enter a true "hibernation" but rather a state of torpor. To myself, it doesn't matter how they classify the bear's winter nap. It is interesting to see what the expression of genes can do to keep a bear alive through the winter. When reading this article, I felt like I was reading science fiction. The bear had the ability to make it's heart slow down, keep itself from losing muscle, and even make itself stop producing waste.

https://www.sciencedirect.com/science/article/abs/pii/S1043276009001568
https://bear.org/do-black-bears-hibernate/
https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-12-171

Do Genes Control Your Sleep?

Recent studies suggest that sleeping too much or sleeping too little could be genetically linked. Abnormal sleeping patterns are connected to the regulation of thyroid hormone levels, specifically the DNA region located close to the PAX8 gene. Excessive sleepers are those who sleep more than 10 hours a day, and this condition is called hypothyroidism which occurs when the thyroid glands do not produce enough thyroid hormones. Hyperthyroidism is when too many thyroid hormones are produces which  results in insomnia, and those affected sleep less than 6 hours a day.

There is another sleeping pattern where people can function normally with only 4-6 hours of sleeping. This sleep pattern is a result of a mutation in the DEC2 gene, and typically expressed as falling asleep between 11pm and midnight, and waking up as early as 4 pm. This mutation results in alertness decreasing late at night allowing individuals to fall asleep faster, and waking you up alert and ready in the early morning. This mutation is rare, but different sleep patterns are controlled by different genes.

Studying the Genetic Basis of Sleep Patterns in Fruit Flies

Humans have a very distinct differentiation in the required amount of sleep people need to function for the following day. This variation in humans is not unique, and even Drosophila melanogaster exhibit variations in sleep patterns as well. The ability to understand the genetic basis of sleep could help to identify molecular mechanisms that are essential in heredity of this trait. Researchers published an article on the website Genes|Genomes|Genetics, where researchers described a collection of inbred fruit flies that exhibit extreme sleep behaviors that would help them to ultimately determine the genetic basis of sleep needs.

A previous research study had created a population of fruit flies that showed long sleeping and short sleeping traits. Researchers worked with flies from the Drosophila Genetic Reference Panel (DGRP), which is a population of more than 200 inbred lines room Raleigh, North Carolina. Basically, DGRP is a library of fruit flies that have polymorphisms of complex traits. Researchers chose five longest and five shortest sleeping lines from the DGRP an allowed them to randomly cross for 21 generations to produce an outbred population. Using artificial selection, the researchers produced two long sleeping and two short sleeping populations.

From these populations, the new article highlights the researchers creating an inbred lines. Inbred ines are important in genetic studies because it reduces genetic variation. To create the inbred lines, the researchers selected a male and a female from each population and mated them and then selected one male and female fro the progeny to propagate the line. This process repeated for 20 generations and created a total of 39 inbred lines and these were called the Sleep Inbred Panel.

Simple demonstration of the process carried our by the scientists using inbreds

Night sleep of the inbred lines ranged from one hour to almost twelve hours, which demonstrates that the extreme phenotypes of sleep times were maintained in the inbred lines. Phenotypes were similar to the parental populations which demonstrates that inbreeding reduces genetic variability. The only variation between the new flies and the parent flies was due to the short sleeping population, which may have had a lower fitness than the other flies. Overall, the authors identified SNPs and genomic variations with sleep phenotypes that dates back to the DGRP inbred lines.

This research in fruit flies can help researchers determine variation in sleep cycles and sleep processes in humans. Perhaps there is a genetic connection between preference of sleep, like those who enjoy sleeping more in the morning or those that enjoy sleeping more at night and waking up earlier. Going a step further, finding the genetic connection to sleep patterns may help researchers identify the causes of sleep disorders and using some molecular genetics techniques could possibly cure those diseases. Personally, I am able to wake up earlier in the morning and also stay up late at night if possible, and seeing this research done on human genetics could just be an additional insight on how we function as humans and as a society in regards to sleep patterns.

Can't sleep? Could be down to genetics

    

          Just recently, “researchers have identified specific genes that may trigger the development of sleep problems, and have also demonstrated a genetic link between insomnia and psychiatric disorders such as depression, or physical conditions such as type 2 diabetes. Up to 20 percent of Americans and up to 50 percent of US military veterans are said to have trouble sleeping.” Many humans fare faced with insomnia and cannot fall asleep too quickly. This could also be due to stress, work-related issues, family problems, or just heath issues. Discussed in the article “… in this study, Stein’s research team conducted genome-wide association studied (GWAS). DNA sample obtained from than 33,000 soldiers participating in the Army Study To Assess Risk and Resilience in Service-members (STARRS) were analyzed.

         Data from soldiers of European, African and Latino descent were grouped separately as part of efforts to identify the influence of specific ancestral lineages. Stein and his colleagues also compared their results with those of two recent studies that used data from the UK Biobank.” (Springer, 2018). This study conducted had the conclusion that “insomnia has a partially heritable basis. The researchers also found a strong genetic link between insomnia and type 2 diabetes.” (Springer, 2018). Stein says, “The genetics correlation between insomnia disorder and other psychiatric disorders, such as major depression, and physical disorders such as type 2 diabetes suggests a shared genetic diathesis fo these commonly co-occuring phenotypes.” (Springer, 2018). 

Link to study: https://www.sciencedaily.com/releases/2018/03/180309095520.htm

Original study:  https://www.nature.com/articles/s41380-018-0033-5

Springer. (2018, March 9). Can't sleep? Could be down to genetics: Large study confirms that insomnia is hereditary. ScienceDaily. Retrieved May 3, 2018 from www.sciencedaily.com/releases/2018/03/180309095520.htm

Are You A Night Owl?

     Many of us have heard the term "night owl," however do genetics contribute to the late night behavior? Staying up late and having trouble waking up is often diagnosed as delayed sleep phase disorder (DSPD) according to sleep clinicians. It is estimated to affect about 15% of the population in the United States. People with DSPD have a delayed circadian rhythm, which in your internal clock aligning with the physiology of the environment. People's circadian rhythm have a clear genetic basis that has remained the same over the course of evolutionary history. In cases of people with DSPD, there is a large part of the protein expressed by the gene to be missing. This change makes the inhibitor hyperactive, causing it to repress the activators for too long and extend the circadian cycle by at least a half an hour if not more.
     Fortunately, I am not part of the 15% of night owls. In fact, I am the complete opposite. I have a very hard time staying up late, and find myself fatigued throughout the day. I am a very early riser, having no trouble at all hopping out of bed as soon as my alarm sounds. However, I must do farther research on this topic, as it pertains to my boyfriend. He on the other hand, cannot fall asleep early, and cannot wake up at a decent hour. Now he can make the valid argument that it is not laziness, but genetics causing this behavior!

Night Owls
Internal Clock

Are you a 'night owl'? You may have this genetic mutation

This article is about how a single point mutation in the DNA sequence can have an effect on your sleeping patterns. More specifically, your circadian rhythm. The gene with the mutation is CRY1 and this affects the suppressors of the individuals circadian rhythm. This can extend their cycle by at least a half an hour, which can lead to a state of " perpetual jet lag". This isn't an impossible thing to get past though, just requires a stricter sleeping schedule.

My opinion is that this is interesting to learn about, mainly because I am one of these people. On the positive side, it is easier to get past the difficulties if there is enough motivation to get up, like getting something to eat.

Medical News Today

Circadian Rhythm 

Researchers at 23andMe Determine Sleeping In Longer is Genetic

Figure 1. An adorable sleeping baby

23andMe has recently utilized their database to analyze 89,000 DNA sequences of people to determine if waking up early or sleeping in late is due to genetics. In addition to analyzing the DNA sequences, the profiles of each participant was analyzed to determine there characteristics such as sex, age, and illnesses. Through this data, the researchers have come to the conclusion that people that are female, are over 60 years old or are not suffering from insomnia are more likely to not stay up late and feel fine with waking up early. The opposite characteristics were true with people who stayed up late and slept in longer. However, this data is not 100% conclusive due to the fact that only people of European descent were studied, but it does provide substantial evidence due the vast number of participants.

I have always believed that this trait to be due to genetics, and I am not surprised that the data collected by 23andMe supports it. It would be interesting to see the if the researches would eventually be able to create better drugs to help people go to sleep and feel well rested when they wake. Or the possibility of a "Power Nap" pill where it would make a 30 minute nap equivalent to an 8 hour sleep. This would have a heavy impact on how the world worked because people would be able to work more and longer and still have many more hours in the day for family and spending the extra money they are making which would in turn boost the economy. This is a bit of a far fetched idea, but I believe we are one step closer to it with the new findings of the researchers.

I Can’t Help It, It’s In My Genes

As the old saying goes, “The early bird catches the worm.” However, some people, maybe even yourself, feel best staying up late and sleeping in vs getting up at the crack of dawn. According to a recent study published in Nature Communications, a human’s preference for early mornings or late nights might come down to the individuals genes.

This study, which was commissioned by 23andMe, utilized their massive genetic database to analyze DNA from more than 89,000 people. In addition to sending in their spit, participants of this study also answered a two-part online survey, which categorized them as morning or evening people based off their self-reporting answers. From the participants’ profiles, researchers of this study were able to make some conclusions on what they believed were characteristics that most likely lead to being a morning person. These were being a female, being over 60yrs old, having a healthy BMI, not suffering from insomnia, and being able to feel well-rested off less than 8hrs of sleep.

This study initially generated a lot of excitement because the conclusions had been drawn from a large number of humans, making the results more robust and significant. However, the population used was only European descent, which itself paints a skewed picture. In addition, self-reporting from the patients was used as well, which is notoriously known for inaccurate numbers. Regardless, the spots identified on the genome by researchers will prove to be useful for future studies.

This article was interesting because it covered a topic that is near and dear to many college students; why is it so hard to get up for 8:00am classes? It is funny to find out that it may be because of our genes. Besides when I stay up really late, I am definitely a morning person, which both my mother & father 100% are. However, since there were flawed components to the study, there is definitely room for improvement. I look forward to when scientists smooth out the bumps.

http://www.popsci.com/not-an-early-bird-blame-it-on-your-genes
http://www.nature.com/ncomms/2016/160202/ncomms10448/full/ncomms10448.html#affil-auth