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Did you know that our ancestors were nocturnal? They used to stay awake in the night to hunt without worrying about dangerous predators and sleep during the day. Now, our circadian rhythms are lined up with the sun. That's why as soon as the sun sets, our bodies start getting ready for rest, and we end up feeling sleepy.
Circadian rhythms are biological cycles that coordinate essential mental and physical functions, such as sleep and hunger. The circadian clock is regulated by a part of the brain called the Suprachiasmatic Nucleus (SCN).
The circadian clock is also influenced by temperature. When the body temperature drops around the afternoon and late evening, it induces drowsiness and sleep.
Sleep is induced by a hormone called melatonin, which is produced in low-light conditions. Bright light conditions during the day suppress melatonin production and promote wakefulness.
People who work the night shift have disrupted circadian rhythm and have an increased risk for the following conditions:
Working the night shift is carcinogenic to humans, according to multiple studies conducted the world over.
Several studies show that disruption in the night’s sleep can reduce melatonin levels and increase the risk of tumor growth.
Some animal studies have shown that exposure to light at night led to the growth of breast cancer.
The risk of breast cancer among nurses and other night-shift workers seems to be higher than their counterparts who worked day shifts.
A study published in the Journal of National Cancer Institute in 2001 reported that women who work in rotating night shifts for at least three nights per month, along with day shifts, have a moderately high risk of breast cancer.
Further, the risk seems to be higher when the night shifts per week increase!
This increased risk is attributed to the messed-up melatonin levels in the body.
In addition to promoting sleep, melatonin also stops tumor growth and protects against the spread of cancer cells.
When melatonin levels decrease in the body, it results in an imbalance of inflammatory cytokines, increased mutations in the cells, and oxidative damage (due to free radicals).
These events can all trigger cancer development.
A reduction in melatonin also affects estrogen levels, which further increases the risk of breast cancer.
A long duration of shift work throughout the years is associated with estrogen and progesterone-positive tumors.
When the circadian rhythm is altered, it changes the expression of the CLOCK genes. This also influences the production of reproductive hormones.
The Neuronal PAS Domain Protein 2 or NPAS2 gene is the largest circadian gene. It plays a vital role in sleep homeostasis and circadian rhythm regulation.
This gene also regulates the cell cycle and works with certain other genes for repairing DNA. The NPAS2 gene shows a strong association with breast cancer.
rs2305160 (Ala394Thr) is an SNP (Single Nucleotide Polymorphism) in the NPAS2 gene.
Among women with little or no exposure to shift work, the A allele (AA or AG) is associated with a significantly lower risk of breast cancer.
However, among women with AA genotype who had worked >2 years of rotating night shifts, the risk of breast cancer was nearly 3 fold compared to women with the same genotype with <2 years of night shift work.
| Genotype | Implication - > 2 years of rotating night shifts |
| AA (Thr/Thr) | ~3 fold increased risk of breast cancer |
| AG (Thr/Ala) | Slightly increased risk of breast cancer |
| GG (Ala/Ala) | Normal risk of breast cancer |
Use Xcode Life’s Free Gene Tool To Find Out If You Have The Risk Genotype!
RAR-Related Orphan Receptor A or the RORA gene is located on chromosome 15 and regulates genes involved in the body’s circadian rhythm.
rs1482057 is an SNP in the RORA gene. A study published in 2014 showed that SNP rs1482057 was associated with breast cancer in postmenopausal women.
Women who have at least one A allele and had a history of working night shifts in their lifetime had a higher risk of developing breast cancer.
Conversely, women having the CC genotype and working night shifts showed a decreased risk of breast cancer.
| Genotype | Implication |
| AA | Increased breast cancer risk on night shift work |
| AC | Increased breast cancer risk on night shift work |
| CC | Decreased breast cancer risk on night shift work |
Cryptochrome circadian regulator 2 or the CRY2 gene gives instructions to produce a protein involved in regulating the body’s circadian rhythm.
rs2292912 is an SNP in the CRY2 gene, located on chromosome 11. Night shift working increased the risk of breast cancer in women who carried the CG genotype of rs2292912 SNP.
| Genotype | Implication |
| CG | Increased breast cancer risk on night shift work |
| GG | Decreased breast cancer risk on night shift work |
| CC | Decreased breast cancer risk on night shift work |
Since working night shift hours increases the risk of breast cancer in women, one of the most effective ways to lessen this risk is to reduce working night shifts.
Switching with a colleague’s shift, alternating your night shifts with day shifts, or switching jobs can be a few ways by which you can reduce your night shift hours.
Apart from disrupting the sleep-wake cycle, disturbed sleep or poor quality of sleep in people who work night shifts can increase their risk for breast cancer.
So, if you are working a night shift, ensure you get your 7-8 hours of sleep every day. If you have trouble sleeping, consult your doctor about supplements that can help you catch up on your daily sleep.
People working the night shift must try and reduce other risk factors of breast cancer.
A healthy diet with lots of fruits, limited alcohol consumption and smoking, adequate physical activity, and reduced exposure to harmful chemicals can help reduce breast cancer risk.
Night shift work can impact your circadian rhythm by making you operate in a way that is “unnatural” to your sleep-wake cycle. A recent study has reported that people who work night shifts are at an increased risk of developing atrial fibrillation and heart disease. The study further reported that among the night shift workers, women who are physically inactive are at the highest risk.
Atrial fibrillation (AF) is characterized by irregular and often rapid heart rate that can increase the risk of stroke, heart failure, and other heart-related ailments.
Generally, the chambers of the heart work in coordination to pump the blood. However, in AF, the two upper chambers of the heart (right auricle and left auricle) beat chaotically and out of coordination with the two lower chambers (right and left ventricle) of the heart.
Some common symptoms associated with AF include :
Learn Your Genetic Risk for Atrial Fibrillation with Xcode Life’s Gene Health Report
Night shift workers, on average, get two to three hours less sleep than other workers. They often sleep through the day in two split periods; a few hours in the morning and then around an hour before starting the night shift.
It’s challenging to keep the sleep environment dark, free of noise, and relatively calm. A person working the night shift is at greater risk of various health conditions due to the disrupted circadian rhythm.
Researchers suggest that working the night shift may lead to hormonal and metabolic changes, which can increase the risk for obesity, diabetes, and heart disease.
Further, studies report that circadian misalignment results in a drop in levels of the weight-regulating hormone leptin. This can increase heart disease risk by prompting an increase in appetite.
The study included 286,353 people who were in paid employment or self-employed.
The study cohort was divided into:
The researchers adjusted their analyses for several factors like age, sex, ethnicity, education, socio-economic status, diet, smoking, body mass index, sleep duration, and chronotype that could alter the risk of developing AF.
The researchers, therefore, adjusted these risk factors.
The following were observed in the study:
The study further revealed two more interesting findings.
Avoid Caffeine Close to Bedtime
Caffeine inhibits your body’s ability to feel sleepy. So, avoid food and drink containing caffeine at least 4 hours before your bedtime.
Maintain A Sleep-Conducive Environment In Your Bedroom
Light exposure can activate all the processes in your body associated with wakefulness, making it difficult for you to fall asleep. Use blackout curtains or blinds that can help block the light entry.
Eat Healthy
Shift work has been associated with an increased risk of metabolic disorders. Limit sugar intake and increase protein intake. Eating small, frequent meals can also help maintain your metabolic health.
Exercise Regularly
Avoid daytime exercising when on shift work, as it can promote wakefulness. But, make sure to adopt a consistent exercise routine as this can help lower the risk for heart disease.
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 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.
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.
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.
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.
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 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.
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.
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.
https://pubmed.ncbi.nlm.nih.gov/32060260/
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
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.
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.
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.
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.
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/
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.
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.
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
Summary
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/
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 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.
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
Summary
References:
https://pubmed.ncbi.nlm.nih.gov/32060260/
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.
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.
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
TipsTo Prevent And Manage Insomnia
Summary
References
https://pubmed.ncbi.nlm.nih.gov/30804565/
https://pubmed.ncbi.nlm.nih.gov/26132482/
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).
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.
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.
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.
https://pubmed.ncbi.nlm.nih.gov/31817803/
https://pubmed.ncbi.nlm.nih.gov/15965471/
