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.
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.
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|
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.
Conversely, women having the CC genotype and working night shifts showed a decreased risk of breast cancer.
|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.
|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.
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 :
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.
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.
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.
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.
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.
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.
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
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
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:
- Low energy
- Loss of appetite
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
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
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
Narcolepsy is a sleep disorder that is characterized by five symptoms:
1. Excessive daytime sleepiness
2. Cataplexy (sudden muscle weakness that occurs without any 'warning')
3. Sleep paralysis (a state of awareness with an inability to speak or move - usually occurs during waking up or falling asleep)
4. Hypnagogic hallucinations (vivid dreamlike experiences),
5. Disturbed nocturnal sleep
It affects approximately 1 in 2000 individuals and usually appears during childhood or early puberty.
There are two major types of narcolepsy:
Type 1 narcolepsy (NT1) : It is characterized by excessive daytime sleepiness as well as cataplexy. People with NT1 have lower levels of a brain hormone called hypocretin.
Type 2 narcolepsy (NT2) : Nt2 is a type of narcolepsy without cataplexy. People with NT2 have normal levels of hypocretin.
How Does Genetics Influence the Risk Of Narcolepsy?
The heritability among monozygotic twins for NT1 was found to be 20-30%.
If a first-degree family member has NT1, your risk for NT1 increases by 10-40 times. This shows that there are some genetic and environmental factors that play an important role in narcolepsy.
There are multiple genes that are associated with NT1, but almost all patients with NT1 carry a specific variant of the human leukocyte antigen (HLA).
HLA system regulates immune functioning in the body.
The currently identified genetic factors do not fully reveal the heritability of narcolepsy.
However, narcolepsy has been associated with a significant reduction in orexin producing neurons in the brain. Orexin is a neurotransmitter that is considered the master regulator of the sleep-wake cycle. A deficiency of orexin-producing neurons can cause narcolepsy.
The P2RY11 gene is a member of the G-protein coupled receptors family, expressed by the immune cells. It plays an essential role in immune functioning and cell death regulation.
Variations in the P2RY11 gene might dysregulate the functioning of certain immune cells like CD8+T-cells and contribute to the development of narcolepsy.
The rs2305795 is a G>A polymorphism located in the P2RY11 gene on chromosome 19.
A study documented that the rs2305795 A allele is associated with a reduced immune response to infectious triggers, thereby contributing to narcolepsy risk.
Non-genetic Influences On Narcolepsy Risk
Some risk factors for narcolepsy include:
- Autoimmune effects
- Upper airway infection
- Head injury
- Age (10-30 years)
Effects of Narcolepsy on Health
TipsTo Manage Narcolepsy
There is no cure for narcolepsy, but certain lifestyle changes and treatments can help you manage it.
1. Try to stick to a sleep schedule, including short naps for about 20 minutes during the day.
2. Avoid alcohol, nicotine, and caffeine consumption, especially at night, and eat healthily.
3. Include some exercise in your daily routine to make you feel more awake during the day and tired at night.
4. Try to avoid activities that may be dangerous if you fall asleep suddenly, like driving or get enough sleep before you do that activity if necessary.
5. Talk to everyone you work with about your condition. They need to be informed so that they can help you if needed and know how to react.
6. Your doctor may prescribe stimulant medicines to help you stay awake during the day and antidepressants to help with the nightmares and hallucinations.
7. Counseling and support groups can help you relieve your emotions and deal better with the condition.
Sleep efficiency refers to the percentage of time a person sleeps to the amount of time a person spends in bed. It is calculated by the ratio of the total time spent asleep (TST) in a night compared to the total amount of time spent in bed. An efficient sleep leads to a deeper sleep of better quality with lesser disturbances that may result in good stamina and sufficient rest upon waking, while an inefficient sleep may lead to uneasiness and fatigue.
Sleep Efficiency Rates
Sleep efficiency rates tend to vary from person to person. Normal sleep efficiency is considered to be 80% or greater. For example, if an individual spends 8 hours in bed, at least 6.3 hours or more should be spent sleeping to achieve 80% or greater sleep efficiency. Most healthy and young adults have sleep efficiencies above 90%.
How Does Genetics Influence Sleep Efficiency?
UFL1 is one of the genes in the ubiquitin pathway - the principal mechanism behind protein breakdown.
This pathway has also been implicated in schizophrenia, a condition in which poor sleep efficiency is a common symptom.
The relevance of this pathway in sleep disturbances was further explored in another study.
The study indicated that the expression of a protein UFM1, a part of UFL1, increased after partial sleep restriction.
A GWAS analysis found a significant correlation between a variant (rs75842709) near the UFL1 gene and sleep efﬁciency.
The T-allele was associated with a 5.7% decreased sleep efﬁciency.
Non-genetic Influences Of Sleep Efficiency
Some factors that lower sleep efficiency:
- Higher fatigue
- Less activity during the day
- Light at night
- Jet lag
- Sleep environment
Tips To Improve Sleep Efficiency