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What Is A Chronotype?

Research shows that your bedtime may actually be linked to your DNA! Everyone’s biological clock is wired differently; it’s not in sync. Environmental and genetic factors affect your circadian rhythm, or your internal clock. Circadian rhythms, in turn, influence your sleeping pattern.  

Your preferred sleeping pattern is called your ‘chronotype.’ Going to sleep around 11 PM and waking up around 7 AM puts you in the average chronotype category. Someone with an average chronotype gets roughly the same amount of sleep on both working and non-working days, and this is good.  

About 40% of the population does not belong to this category. They have late or early chronotypes. These people will find it pretty difficult to go to work after a free day. They may even experience symptoms of jet lag.

What contributes to the difference in chronotypes?

Melatonin: The Sleep Hormone

Melatonin is the "sleep hormone" that regulates the sleep-wake cycle in the body. It is produced by a neuron bundle called Suprachiasmatic Nucleus or SCN for short. 

For people with the average chronotype, melatonin production starts around 9 PM, and the whole body enters into the 'rest mode' by 10:30 PM. The body temperature enters its lowest around 4:30 AM. These people usually wake up around 6:45 AM when the blood pressure spikes to the highest point. They are known as the 'early risers' and are alert and active during the daytime. 

For people with the late chronotype, this whole cycle happens later during the day. As a result, they tend to sleep and wake up much later. 

what is a chronotype?

They may not entirely be able to fix this. This is because the CLOCK genes found in the SCN neuron bundle regulate the 24-hour cycle in your body. Changes in the CLOCK genes influence your chronotype status - average, or early, or late.

A study was carried out on hamsters to study the contributing factors to chronotype. Scientists replaced the SCN of early chronotype hamsters with that of average chronotype hamsters. To their surprise, the hamsters still went to sleep and woke up early, according to their early chronotype. 

This is because, other than the SCN clock, the body also contains other biological clocks, all of which contribute to a person’s chronotype. And, this is why it can be very difficult to break out of your natural sleeping pattern. 

Chronotype Genetic Test

To know what your chronotype is based on your genes, you can get a genetic test done. Most genetic tests provide your DNA information in the form of a text file called the raw DNA data. At Xcode Life, can help you interpret this data.

All you have to do is upload your raw data and order a sleep report. Xcode Life then analyzes your raw data in detail to provide you with a comprehensive sleep analysis, including information on your chronotype and risk for various sleep disorders.

Video

Introduction: What Is Snoring?

Snoring is the loud or harsh sound from the nose or mouth that occurs when breathing is partially obstructed. The sound is produced when the soft palate and other soft tissues (such as uvula, tonsils, nasal turbinates, and others) in the upper airway vibrate.

Affecting nearly 90 million Americans, it can lead to disturbed, unrefreshing sleep, ultimately resulting in poor daytime function. Snoring is caused due to obstruction of air passage, resulting in the vibration of respiratory structures and the production of sound during breathing while asleep.

Snoring is more prevalent in males than in females. Certain risk factors such as genetic predisposition, throat weakness, obesity, mispositioned jaw, obstructive sleep apnea, sleep deprivation, alcohol consumption, and mouth breathing are associated with snoring.

How Do Genes Influence Snoring Risk?

Twin and family studies have identified the association between genetic factors and snoring risk, with heritability ranging between 18 to 28%.

A recent study published in 2019 leveraged data from a large U.K. Biobank study consisting of the Australian adult population to identify the molecular mechanisms associated with snoring.

MSRB3 Gene and Snoring

MSRB3 is associated with protein and lipid metabolism pathways, which are related to hippocampal volume (a region in the brain) and lung function. Such genetic associations are consistent with the findings that severe bouts of snoring may be due to:
- Nocturnal oxygen desaturation (temporary drop in oxygen levels in hemoglobin)
- Lowered neuropsychological functions, with reduced ability to consolidate memory.

rs10878269 And Snoring

The rs10878269 is G>A polymorphism located in the MSRB3 gene. A study by Jones, Samuel E., et al.2016 showed that variant rs10878269 was significantly associated with reduced snoring risk.

Non-genetic Influences On Snoring

Effects Of Snoring

Snoring is not often considered a serious health concern except in some conditions. Snoring can usually be cured through simple home remedies. Light and infrequent snoring is completely normal. Snoring that is linked to obstructive sleep apnea (OSA) is, however, worrisome and needs to be treated.

Tips For A Snore-free Sleep

  1. Reduce the consumption of alcohol and sedatives as this relaxes your muscles and leads to snoring.
  2. Maintain your weight as obesity and being overweight are risk factors for snoring and sleep apnea.
  3. Change your sleeping position. When you sleep on your back, your airway has higher chances of getting blocked. Sleeping on your side, raising your head by a few inches, or using a pillow to improve your neck position are a few alternative sleep positions to try.
  4. Relieve nasal congestion before you sleep.
  5. Anti-snoring mouthpieces can be used to hold your jaw and tongue in a suitable position to prevent blockage of the airway,
  6. Throat exercises can help strengthen the muscles and prevent them from collapsing during sleep.
  7. Try to quit smoking. Smoking can result in inflammation in the upper airway passage, and this blocks airflow.

Video

Summary

  1. Snoring is a common sleep disorder that affects over 90 million Americans. It is characterized by a loud noise from the nose/mouth due to an obstructed airway.
  2. Genetic predisposition, throat weakness, obesity, mispositioned jaw, obstructive sleep apnea, sleep deprivation, alcohol consumption, and mouth breathing are some risk factors associated with snoring.
  3. The MSRB3 gene, associated with protein and lipid metabolism pathways related to lung function and hippocampal volume, affects sleep-related snoring. The rs10878269 SNP, a G>A polymorphism, is associated with a reduced risk of snoring.
  4. Snoring is not a serious health concern unless linked to other sleep disorders like Obstructive Sleep Apnea(OSA).
  5. Changing your sleeping position, maintaining a healthy weight, reduced alcohol consumption and smoking, and throat exercises are some of the recommendations to have a snore-free sleep at night.

References

https://pubmed.ncbi.nlm.nih.gov/32060260/

What makes a person an early riser or a night owl?

Chronotype is influenced by differences in circadian rhythm, which refers to the fundamental 24-hour physiological cycle essential for various molecular and behavioral processes. It helps regulate sleep patterns.

The timing of circadian rhythms varies across individuals and is influenced by both environmental and genetic factors. People with earlier rhythms tend to rise early in the morning and feel sleepy earlier in the night. If your body sides with the “morning clock” then you are a “morning person.” The other end of this spectrum has people with delayed rhythms. They tend to sleep and wake up late and are often referred to as an “evening person” or a “night owl.”

Research has shown that morning people are more focused, persistent, agreeable, plan their future better, and are less likely to smoke and drink or get depressed. They may exhibit characteristics like:
- Waking up early
- Being more active during the morning hours
- Being more focused and happy
- Being more productive during the day

Similarly, night owls enjoy a burst of strength during the night and may exhibit characteristics like:
- Waking up late
- Being more active during the evening hours
- Being more creative and adventurous
- Being more productive during the night

How Does Genetics Influence Circadian Rhythm?

A GWAS study of self-reported chronotype (morning/evening person) of UK Biobank data identified 22 regions in the circadian rhythm and photo-reception genes associated with morningness. This was also replicated in a 23andMe study.

One of the strongest associations was seen in the rs516134 SNP located near the RGS16 gene.

RGS16 Gene and Circadian Rhythm

The RGS16 gene encodes a protein that belongs to the regulator of G protein signaling. This protein is responsible for turning off certain signal communications between cells in the body.

Microarray studies and gene expression analysis have demonstrated that the RGS16 gene exhibits circadian variations. According to a study, mice lacking this gene have a longer circadian period.

rs516134 SNP and Morningness

The rs516134 is a C>T polymorphism located in the RGS16 gene. The C allele is found to be strongly associated with morningness.

Non-genetic Influences On Circadian Rhythm

A study found that morningness is significantly associated with gender, with a prevalence of 39.7% in males and 48.4% in females.

Also, people over 60 were more likely to prefer mornings than people under 30 - meaning people’s sleep preferences may change over time.

Effects of Circadian Rhythms

Circadian rhythms affect day-to-day bodily functions such as sleep, eating habits, hormones release, and body temperature.
Many studies have documented that irregular rhythms are linked to various chronic conditions such as sleep disorders, obesity, depression, diabetes, hypertension, bipolar, and schizophrenia.
It is known that the vast majority of patients with depression have sleep abnormalities; either they sleep too much or have insomnia and can’t sleep at all.
Several genetic variants are correlated with how circadian rhythms function and their association with health conditions.
The interplay between genetics and non-genetic factors (such as sunlight, eating habits) with circadian rhythm is clear.
Maintaining a routine with a balanced lifestyle may help to stabilize the internal biological clock and health.

Tips To Become An Early Riser

  1. Sleep early and shift your bedtime gradually to get about 7-9 hours of sleep.
  2. Stay consistent with your timings. Set your alarm clock to the same time every morning to make it easier to get into a routine.
  3. Move your alarm clock to a distance where you would have to get up to turn it off. There are a few apps like Smart Alarm or Math Alarm which require you to do an activity to turn off the alarm. This will help you stay awake and not snooze your alarm and go back to sleep.
  4. Exposure to bright light in the morning, especially natural light, helps make you alert and gets you used to wake up early. Your body’s circadian rhythm is responsive to light and dark conditions.
  5. Get active in the morning and go for a jog or run. You can even hit the gym in the morning and finish your workout. This will give you the energy to start your day.
  6. Think about the various reasons why waking up in the morning could be beneficial and how you can be more productive during the day.
  7. Use something to look forward to in the morning as bait to wake up for. A cup of hot coffee, a nice breakfast, a puzzle in the newspaper are a few of the things that you could look forward to.
  8. A protein-heavy meal is said to increase your dopamine levels, facilitating wakefulness, and making you ready for the day.

Summary

  1. Circadian rhythm, which refers to the fundamental 24-hour physiological cycle essential for various molecular and behavioral processes, helps regulate your sleep patterns.
  2. People with earlier rhythms are termed as morning people, whereas those with delayed rhythms are termed as night owls. Morning people are known to be more focused and happy, while night owls are known to be more creative and adventurous.
  3. Both environmental and genetic factors influence your sleep patterns.
  4. Several genes are known to affect circadian rhythm. The C allele of the rs516134 SNP in the RGS16 gene, which is involved in turning off certain signals between cells in the body, is known to be strongly associated with morningness.
  5. Circadian rhythms affect your day-to-day functions, and irregularity is associated with chronic health conditions.
  6. Following a routine with a balanced and healthy lifestyle can help set your biological clock right.

References:

https://pubmed.ncbi.nlm.nih.gov/27494321/
https://pubmed.ncbi.nlm.nih.gov/26835600/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428740/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018537/

Introduction

Sleep is a critical component of optimal health. A healthy sleep comprises various aspects, including adequate duration, good quality, and the absence of sleep disorders. Inadequate sleep at night is generally associated with:
- Daytime sleepiness
- Daytime fatigue
- Depressed mood
- Poor functioning
- Other health issues

Sleep duration refers to the total amount of sleep obtained either during the nighttime sleep event or across the 24-hr period.

Importance of An Adequate Sleep

Getting enough sleep at night is very important for several reasons. Sleep is linked to your mental and physical health and quality of life. When you get adequate sleep at night, you can be more productive and concentrate better during the day. It reduces your risk of heart disease and prevents depression. Your immune system becomes stronger as sleep helps the body to repair and recover. Your athletic performance can also be improved because of a good night’s sleep. Not getting enough sleep can make you gain weight faster.

RDA: What Is The “Ideal” Sleep Duration?

National Sleep Foundation guidelines recommend 7-9 hours of sleep per night for healthy adults. Babies, young children, and teens need even more sleep to enable their growth and development. People over 65 should also get 7 to 8 hours of sleep per night.

How Does Genetics Affect Sleep Duration?

Studies have shown that certain genetic variants influence habitual sleep duration, which explains why some individuals need more sleep than others.
Twin studies have shown that the heritability estimation of sleep duration is around 10 - 40%.

A GWAS study of self-reported chronotype and sleep duration of UK Biobank data identified several genetic regions associated with sleep duration. This study documented that people with genetic variants for longer sleep duration reported an average of 22 minutes more sleep.

PAX8 Gene and Sleep Duration

The PAX8 gene encodes a member of the paired box (PAX) family of transcription factors involved in thyroid follicular cell development and the expression of thyroid-specific genes.

Variations in the PAX8 gene may affect different functions, including DNA binding, gene activation, and protein stability.

Research studies have found that the sleep-wake cycle may be influenced by regulating thyroid hormone levels. Individuals with hypothyroidism (a condition in which the thyroid gland does not produce enough thyroid hormones) are prone to excessive sleepiness. People with hyperthyroidism (in which the thyroid makes too much of the hormone), on the other hand, may have insomnia.

rs62158211 And Sleep Duration

The rs62158211 is a G>T polymorphism located in the PAX8 gene. The T allele is associated with longer sleep duration.
A study documented that the rs62158211 was associated with an average 2.6-minute per-allele change in sleep duration.

Non-genetic Influences On Sleep Duration

Some risk factors that lead to shorter sleep duration include alcohol consumption, smoking, and physical inactivity.

Effects of Sleep Duration on Health

Few epidemiological and genetic studies have demonstrated a strong biological link between abnormal sleep duration, risk of schizophrenia, type 2 diabetes, fetal growth, and Crohn's disease.

Sleep duration is also associated with cardiovascular diseases, type 2 diabetes, depression, automobile and workplace accidents, learning and memory problems, and prospective mortality.

TipsTo Become An Early Riser

  1. Sleep early and shift your bedtime gradually to get about 7-9 hours of sleep.
  2. Stay consistent with your timings. Set your alarm clock to the same time every morning to make it easier to get into a routine.
  3. Move your alarm clock to a distance where you would have to get up to turn it off. There are a few apps like Smart Alarm or Math Alarm which require you to do an activity to turn off the alarm. This will help you stay awake and not snooze your alarm and go back to sleep.
  4. Exposure to bright light in the morning, especially natural light, helps make you alert and gets you used to waking up early. Your body’s circadian rhythm is responsive to light and dark conditions.
  5. Get active in the morning and go for a jog or run. You can even hit the gym in the morning and finish your workout. This will give you the energy to start your day.
  6. Think about the various reasons why waking up in the morning could be beneficial and how you can be more productive during the day.
  7. Use something to look forward to in the morning as bait to wake up for. A cup of hot coffee, a nice breakfast, a puzzle in the newspaper are a few of the things that you could look forward to.
  8. A protein-heavy meal is said to increase your dopamine levels, facilitating wakefulness, and making you ready for the day.

Summary

  1. Sleep duration refers to the total amount of sleep obtained during the nighttime sleep event or across the 24-hr period. Getting enough sleep at night is necessary for both mental and physical well-being.
  2. For healthy adults, 7-9 hours of sleep is recommended. Babies, children, and teens tend to sleep for much longer.
  3. Genetics is found to influence sleep duration. The PAX8 gene, which plays a role in thyroid development, is associated with the sleep cycle. The regulation of thyroid hormone levels affects the sleep-wake cycle. The T allele of the rs62158211 SNP in this gene is associated with longer sleep duration.
  4. Certain risk factors like smoking, alcohol consumption, and physical inactivity lead to decreased sleep duration.
  5. Abnormal sleep duration is linked with the risk of schizophrenia, type 2 diabetes, fetal growth, and Crohn's disease.
  6. Exercising during the day, following a proper sleep routine, reducing alcohol consumption and smoking, a comfortable environment, and less frequent napping are some of the things that can make your sleep duration normal.

References:

https://www.sleepfoundation.org/articles/how-much-sleep-do-we-really-need
https://pubmed.ncbi.nlm.nih.gov/27992416/
https://pubmed.ncbi.nlm.nih.gov/27494321/
https://pubmed.ncbi.nlm.nih.gov/25469926/

Introduction: What Is Snoring?

Snoring is the loud or harsh sound from the nose or mouth that occurs when breathing is partially obstructed. The sound is produced when the soft palate and other soft tissues (such as uvula, tonsils, nasal turbinates, and others) in the upper airway vibrate.

Affecting nearly 90 million Americans, it can lead to disturbed, unrefreshing sleep, ultimately resulting in poor daytime function. Snoring is caused due to obstruction of air passage, resulting in the vibration of respiratory structures and the production of sound during breathing while asleep.

Snoring is more prevalent in males than in females. Certain risk factors such as genetic predisposition, throat weakness, obesity, mispositioned jaw, obstructive sleep apnea, sleep deprivation, alcohol consumption, and mouth breathing are associated with snoring.

How Does Genetics Influence Snoring Risk?

Twin and family studies have identified the association between genetic factors and snoring risk, with heritability ranging between 18 to 28%.

A recent study published in 2019 leveraged data from a large U.K. Biobank study consisting of the Australian adult population to identify the molecular mechanisms associated with snoring.

MSRB3 Gene and Snoring

MSRB3 is associated with protein and lipid metabolism pathways, which are related to hippocampal volume (a region in the brain) and lung function. Such genetic associations are consistent with the findings that severe bouts of snoring may be due to:
- Nocturnal oxygen desaturation (temporary drop in oxygen levels in hemoglobin)
- Lowered neuropsychological functions, with reduced ability to consolidate memory.

rs10878269 And Snoring

The rs10878269 is G>A polymorphism located in the MSRB3 gene. A study by Jones, Samuel E., et al.2016 showed that variant rs10878269 was significantly associated with reduced snoring risk.

Non-genetic Influences On Snoring

Effects Of Snoring

Snoring is not often considered a serious health concern except in some conditions. Snoring can usually be cured through simple home remedies. Light and infrequent snoring is completely normal. Snoring that is linked to obstructive sleep apnea (OSA) is, however, worrisome and needs to be treated.

Tips For A Snore-free Sleep

  1. Reduce the consumption of alcohol and sedatives as this relaxes your muscles and leads to snoring.
  2. Maintain your weight as obesity and being overweight are risk factors for snoring and sleep apnea.
  3. Change your sleeping position. When you sleep on your back, your airway has higher chances of getting blocked. Sleeping on your side, raising your head by a few inches, or using a pillow to improve your neck position are a few alternative sleep positions to try.
  4. Relieve nasal congestion before you sleep.
  5. Anti-snoring mouthpieces can be used to hold your jaw and tongue in a suitable position to prevent blockage of the airway,
  6. Throat exercises can help strengthen the muscles and prevent them from collapsing during sleep.
  7. Try to quit smoking. Smoking can result in inflammation in the upper airway passage, and this blocks airflow.

Summary

  1. Snoring is a common sleep disorder that affects over 90 million Americans. It is characterized by a loud noise from the nose/mouth due to an obstructed airway.
  2. Genetic predisposition, throat weakness, obesity, mispositioned jaw, obstructive sleep apnea, sleep deprivation, alcohol consumption, and mouth breathing are some risk factors associated with snoring.
  3. The MSRB3 gene, associated with protein and lipid metabolism pathways related to lung function and hippocampal volume, affects sleep-related snoring. The rs10878269 SNP, a G>A polymorphism, is associated with a reduced risk of snoring.
  4. Snoring is not a serious health concern unless linked to other sleep disorders like Obstructive Sleep Apnea(OSA).
  5. Changing your sleeping position, maintaining a healthy weight, reduced alcohol consumption and smoking, and throat exercises are some of the recommendations to have a snore-free sleep at night.

References:

https://pubmed.ncbi.nlm.nih.gov/32060260/

What is Insomnia?

Insomnia (also known as sleeplessness) is a common sleep disorder that is characterized by the inability to fall asleep or stay asleep at night, resulting in tired or unrefreshing sleep.

According to the American Psychiatric Association (APA), insomnia is the most common sleeping disorder.

Approximately 30% to 40% of adults in the United States report symptoms of insomnia.

A diagnosis of insomnia needs to meet the following two categories:
- Difficulties in sleep for at least three nights a week for a minimum of three months
- Difficulties in sleep that results in functional distress in the individual’s life

This can be caused by variations in biological, psychological, and social factors, which most often result in a reduced amount of sleep.

How Does Genetics Influence Insomnia Risk?

A research study published in 2019 found an association between certain variants in genes like DLG4, LRRK2, DNM1, CRH, GRIN1, DRD1, DRD2, SNCA, DRD4, NTSR1, CNTN2, and CALB1, and insomnia. DNM1 gene codes for the synaptic neuronal protein dynamin 1, which is associated with pre-sleep arousal, a characteristic feature among people with insomnia.

According to a research study, the heritability of insomnia is between 38 to 59%. This suggests a role of genetic factors in insomnia.

Tissue-specific gene-set analyses showed that insomnia might have higher genetic signals among genes that are usually expressed in the brain. The functions of these regions of the brain are of relevance to insomnia.

The genetic correlations between insomnia and psychiatric traits were stronger than the genetic correlations between insomnia and other sleep-based characteristics. According to the study, this suggests that genetically, insomnia resembles neuropsychiatric traits more closely than other sleep-related characteristics.

MEIS1 Gene and Insomnia

The MEIS1 gene is a transcription factor that plays a key role in hematopoiesis, endothelial cell development, and vascular patterning.
It also plays a role in neurodevelopment.
Research studies have shown that the reduced MEIS1 levels and function of the gene may contribute to the pathogenesis of sleep-related disorders.

rs113851554 And Insomnia Risk

The rs113851554 is a G>T polymorphism located in the MEIS1 gene, which is found to be correlated with multiple sleep disorders.
A study found that the T allele of rs113851554 is associated with [an increased risk of developing insomnia symptoms] (https://pubmed.ncbi.nlm.nih.gov/27992416/). Also, functional study analysis suggested that the rs113851554 in the MEIS1 locus is most strongly associated with insomnia disorder.

Non-genetic Influences On Insomnia Risk

Insomnia is more common in women than in men. In fact, women are twice as likely to fall asleep than men. One in four women has some insomnia symptoms.

Insomnia is more common in older people more than men and younger ones. As many as 50% of older adults complain about difficulty initiating or maintaining sleep.

Effects Of Insomnia On Health

  1. Increased risk of heart disease, stroke, inflammation, obesity, seizures, diabetes, and asthma.
  2. Increased risk of anxiety and depression.
  3. A negative impact on your memory.
  4. You find it harder to concentrate and be productive during the day.
  5. Lack of sleep can make you more prone to falling and accidents by affecting your balance.
  6. Insomnia can lower your life expectancy as reported by a study.

TipsTo Prevent And Manage Insomnia

  1. Try to wake up at the same time every day and follow a routine to control your sleep cycle.
  2. Avoid napping during the day for a long time.
  3. Don’t eat right before going to bed and reduce alcohol consumption.
  4. Do some physical activity every day. It helps improve sleep quality and duration.
  5. Reduce your stress before sleeping and set up a comfortable environment.
  6. Massage therapy is known to help people with insomnia sleep better. Meditation can also be helpful.
  7. If lifestyle changes don’t work out for you, consult a doctor to understand the underlying health condition, and take the right medication.

Summary

  1. Insomnia, the inability to fall asleep or stay asleep at night, is the most common sleeping disorder.
  2. This can be caused by variations in biological, psychological, and social factors, resulting in a reduced amount of sleep.
  3. There are genetic correlations between insomnia and psychiatric traits. The MEIS1 gene, known to play a role in neurodevelopment, may contribute to the pathogenesis of sleep-related disorders. The T allele of the rs113851554 SNP is associated with an increased risk of developing insomnia symptoms.
  4. Insomnia is found to be more common in women than in men.
  5. Sticking to a proper routine, exercising, less frequent napping, reducing stress, massage therapy, and reducing alcohol consumption and smoking can help prevent and manage insomnia.

References

https://pubmed.ncbi.nlm.nih.gov/30804565/
https://pubmed.ncbi.nlm.nih.gov/26132482/

Caffeine and Sleep

Caffeine is a central nervous system stimulant, which is widely used for its psychoactive effects. It is commonly used to alleviate behavioral, cognitive, and emotional deficits caused by sleep deprivation.

Regardless of its beneficial effects, caffeine may have adverse sleep-related consequences that might lead to sleep disruption and insomnia symptoms. This is because caffeine consumption is associated with lower levels of 6-sulfatoxymelatonin. 6-sulfatoxymelatonin is a substance produced during the metabolism of melatonin. It is involved in the regulation of circadian rhythm. Lower levels of 6-sulfatoxymelatonin can result in increased alertness (wakefulness).

How Does Genetics Influence The Risk of Caffeine-induced Insomnia?

CYP1A2 encodes cytochrome P-450 group of enzymes. These enzymes influence the absorption and metabolization of caffeine. Caffeine is absorbed rapidly and completely from the gastrointestinal tract. After absorption, the P-450 enzymes help with the metabolization. Variation in the CYP1A2 activity represents a major source of variability in the pharmacokinetics (drug absorption, distribution, metabolism, and excretion) of caffeine.

While the CYP1A2 gene is responsible for caffeine metabolism, another gene, ADORA2A, influences how your sleep is affected by caffeine intake. This gene encodes the adenosine receptor. When an adenosine molecule binds to this receptor, it inhibits all the processes that are associated with wakefulness. Caffeine acts as an adenosine receptor antagonist - it mimics adenosine and goes and binds to the adenosine receptor. This results in increased levels of free adenosine, leading to a boost in neuronal activity and wakefulness.

The adenosine A2A receptor (ADORA2A receptor) plays a role in the effects of caffeine on arousal. Mice lacking functional A2A receptors do not show increased wakefulness in response to caffeine administration, indicating that the A2A receptor mediates the arousal response.

rs5751876 and Caffeine-induced Insomnia

The rs5751876 is a T>C polymorphism located in the ADORA2A gene, which modulates the sleep-wake cycle, and contributes to individual sensitivity to caffeine effects on sleep.
Studies have documented that in caffeine consumers (less than 300mg), rs5751876 - T allele is associated with a decreased risk of sleep complaints and insomnia as compared to the C allele.

Non-genetic Influence on Caffeine-induced Insomnia Risk

  1. Regular consumption - Researchers found that the effects of caffeine on sleep are higher in occasional coffee drinkers compared to those who drink coffee regularly.
  2. Age and weight - Few studies have reported that older adults are more sensitive to the effects of caffeine compared to younger people. The exposure of caffeine in the body may also differ based on the weight of the person.
  3. Time - Consuming caffeine closer to bedtime can disrupt sleep more than when consumed during the day.

Effects of Caffeine-induced Insomnia

If caffeine consumption is not wisely regulated, it could lead to delayed sleep and sleep deprivation. Sleep deprivation is associated with lapses in attention, lowered alertness, and reduction in cognitive function. Scientific studies have shown that a reduction in sleep time of 90 minutes could reduce objective alertness during the day time by one-third.

Tips for Regulating Caffeine Consumption

  1. Moderate your consumption of caffeine. Do not drink caffeinated beverages post 5:00 pm or 5-6 hours before sleeping, as the effects of caffeine last for up to 6 hours after consumption.
  2. Chamomile tea is considered to be a mild tranquilizer or sleep inducer. It contains the antioxidant apigenin, which may promote sleep.

Summary

  1. Caffeine, a central nervous system stimulant, may have adverse sleep-related consequences that might lead to sleep disruption and insomnia.
  2. Genes like CYP1A2 and ADORA2A influence caffeine-induced insomnia. CYP1A2 is related to caffeine metabolism while _ADORA2A influences how your sleep is affected by caffeine intake.
  3. The T allele of rs5751876 SNP in the ADORA2A gene is associated with a decreased risk of insomnia than the C allele.
  4. Age, weight, time of consumption, and frequency of consumption are the non-genetic influences on caffeine-induced insomnia.
  5. Moderated caffeine consumption during the day at least 5-6 hours before sleep is recommended to prevent caffeine-induced insomnia. Chamomile tea can also be consumed as it is a sleep inducer.

Reference

https://pubmed.ncbi.nlm.nih.gov/31817803/
https://pubmed.ncbi.nlm.nih.gov/15965471/

What is Obstructive Sleep Apnea?

Obstructive Sleep Apnea (OSA) is a common, serious, and potentially life-threatening sleep disorder. It is characterized by frequent episodes of partial or complete upper airway obstruction during sleep.
This results in intermittent hypoxemia (low level of oxygen in the blood) and arousal.
Here, the throat muscles relax at irregular intervals and fail to keep the airway open. This results in inadequate breathing for 10 seconds or longer. Thus, the oxygen levels lower, and carbon dioxide levels build up. The brain interprets this as a need to open the airway and wakes you up in the process. This awakening is usually too brief to be remembered. A very noticeable sign of OSA is snoring.

More than 18 million American adults have been estimated to have sleep apnea.

How Does Genetics Influence the Risk of Obstructive Sleep Apnea?

Genes thought to be associated with the development of obstructive sleep apnea are involved in many body processes. They include:
- Communication between nerve cells
- Breathing regulation
- Control of inflammatory responses by the immune system
- Development of tissues in the head and face (craniofacial development)
- The sleep-wake cycle
- Appetite control

African-Americans and Pacific Islanders have more genetic variants associated with sleep apnea than Europeans. Variations in genes such as TNF, CRP, PLEK, PTGER3, LPAR1, HTR2A, and GDNF are associated with the risk of obstructive sleep apnea. Studies suggest that variations in multiple genes, each with a small effect, combine to increase the risk of developing the condition.

TNFA Gene and Obstructive Sleep Apnea

The TNFA gene encodes a proinflammatory cytokine (a molecule released by the T-immune cells) that belongs to the tumor necrosis factor (TNF) superfamily. It regulates various biological processes, including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. Studies have shown that TNF is involved in the regulation of sleep by influencing the adenosine receptor expression.

rs1800629 And Obstructive Sleep Apnea

The rs1800629 is G>A polymorphism located in the TNFA gene associated with increased transcriptional activity and higher TNF levels. This SNP has been studied to contribute to the pathogenesis of sleep disorders. Studies have shown that the rs1800629 - A allele carriers are associated with an increased risk of developing obstructive sleep apnea when compared to G allele carriers.

Non-genetic Influences On OSA Risk

Some non-genetic risk factors for OSA are:
- Narrowed airway
- Smoking
- Hypertension
- Obesity
- Gender
- Menopause
- Diabetes

According to a 2013 study, people with type 2 diabetes have nearly a 50% chance of being diagnosed with OSA. Both of these often coexist because of shared risk factors.

Effects Of OSA on Health

Some effects of OSA that could interfere with everyday functioning include:
- Difficulty in concentrating
- Excessive daytime sleepiness
- Irritability, sexual dysfunction
- Nighttime sweating
- Learning and memory difficulties

Tips for Managing Obstructive Sleep Apnea

  1. Having a consistent sleep cycle routine, maintaining a healthy weight, avoiding smoking and alcohol consumption, a comfortable bedroom environment, and exercise during the day are some of the lifestyle changes that can help prevent and also manage obstructive sleep apnea.
  2. If following lifestyle changes don’t help you manage your sleep apnea, do consult a doctor. This applies to moderate and severe sleep apnea.
  3. The doctor may ask you to use an oral device (mouthpiece) designed to keep your throat open and keep your airway open.
  4. Positive airway pressure treatment reduces the respiratory events that occur when you sleep, thereby reducing snoring also.
  5. In some cases, surgery is also done to manage obstructive sleep apnea.

Summary

  1. Obstructive Sleep Apnea (OSA) is characterized by frequent episodes of partial or complete upper airway obstruction during sleep. Snoring is a notable sign of OSA.
  2. Variations in multiple genes, each with a small effect, combine to increase the risk of developing the condition.
  3. TNFA gene, which encodes a molecule produced by immune cells, is involved in regulating sleep by influencing the adenosine receptor expression. The A allele of SNP rs1800629 is associated with an increased risk of developing OSA compared to the G allele.
  4. OSA can lead to difficulties in concentration, learning, memory, excessive daytime sleepiness, and nighttime sweating.
  5. A consistent sleep cycle routine, healthy weight, and reducing alcohol consumption are some lifestyle changes to help manage OSA. An oral device and positive airway pressure treatment are also used in some cases under the guidance of a medical professional.

References

https://pubmed.ncbi.nlm.nih.gov/22043116/
https://pubmed.ncbi.nlm.nih.gov/23155414/
https://pubmed.ncbi.nlm.nih.gov/20538960/

What is Excessive daytime sleepiness?

Excessive daytime sleepiness (also known as hypersomnia) refers to the inability to stay awake and alert during the normal waking hours that results in unexpected lapses of sleep or drowsiness. It can even occur after long stretches of sleep.

There are two types of hypersomnia; primary and secondary.
Primary hypersomnia occurs without an underlying medical condition. The only symptom is excessive fatigue.
Secondary hypersomnia, on the other hand, occurs due to a medical condition.

Some symptoms of hypersomnia include:
- Anxiety
- Irritability
- Low energy
- Loss of appetite
- Restlessness

A 2019 study in Nature Communications documented that nearly 10–20% of people deal with excessive sleepiness to some degree.

How Does Genetics Influence the Risk of Excessive Daytime Sleepiness?

Studies have shown that certain genetic variants influence daytime sleepiness, which explains why some individuals need more sleep than others. Twin study results have estimated a 38% genetic variance in daytime sleepiness.

Studies have found an association between excessive daytime sleepiness and certain variations in the HCRTR2, PATJ, AR-OPHN1, KSR2,, and PDE4D genes.

The HCRTR2 gene encodes a protein that belongs to the G-protein coupled receptor, involved in the regulation of appetite, energy balance, neuroendocrine functions, and wake promotion.
Latest research studies suggest that variations in the HCRTR2 gene may influence the sleep-wake process.

Non-genetic Influence on EDS Risk

The most common causes of excessive sleepiness include:
- Low sleep duration
- Poor quality sleep
- Sleep deprivation
- Obstructive sleep apnea
- Medications with sedative properties
- Narcolepsy

Research has also indicated that other health conditions can increase the risk of excessive sleepiness. Some of them include:
- High BMI (Obesity)
- Type 2 diabetes
- Depression

Effects Of Excessive Daytime Sleepiness (EDS) on Health

Studies have shown that EDS is associated with an increased risk of developing coronary heart disease and stroke. However, the risk can be managed by improving the quality of sleep.
People with EDS also have poorer health than comparable adults.
According to a study, EDS is associated with negative effects on cognitive function. In fact, EDS is a common symptom in neurological conditions like Parkinson’s and psychiatric conditions like depression.

Tips for Managing Obstructive Sleep Apnea

  1. Having a consistent sleep cycle routine, maintaining a healthy weight, avoiding smoking and alcohol consumption, a comfortable bedroom environment, and exercise during the day are some of the lifestyle changes that can help prevent and also manage obstructive sleep apnea.
  2. If lifestyle changes don’t help you manage your sleep apnea, do consult a doctor. This applies to moderate and severe sleep apnea.
  3. The doctor may ask you to use an oral device (mouthpiece) designed to keep your throat and airway open.
  4. Positive airway pressure treatment reduces the respiratory events that occur when you sleep, thereby reducing snoring also.
  5. In some cases, surgery is also done to manage obstructive sleep apnea.

Summary

  1. Excessive daytime sleepiness refers to the inability to stay awake and alert during the normal waking hours, resulting in unexpected lapses of sleep or drowsiness.
  2. Anxiety, low energy, restlessness, loss of appetite, and irritability are the symptoms of hypersomnia.
  3. The HCRTR2 gene encodes a protein involved in the regulation of appetite, energy balance, neuroendocrine functions, and wake promotion. Variations in this gene may influence the sleep-wake process and influence hypersomnia.
  4. Sleep deprivation, OSA, poor quality of sleep, low sleep deprivation, certain medications, and narcolepsy are some of the non-genetic factors that are associated with insomnia hypersomnia.
  5. Various lifestyle changes can help manage this disease. It can also be treated by treating the underlying cause like sleep apnea.

References:

https://pubmed.ncbi.nlm.nih.gov/31409809/
https://pubmed.ncbi.nlm.nih.gov/27992416/
https://pubmed.ncbi.nlm.nih.gov/29783161/

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