Sleep problems may be caused by lifestyle factors, health conditions, and genetics. If you struggle with insomnia, it is important to understand which genes may play a role. A genetic makeup may influence lifestyle factors and point to specific aspects that need to be addressed. Read on to learn the genetics of your circadian rhythm and sleep requirements.
Genes that Control Sleep Length and Requirements
The Genetic Circuit That Controls Circadian Rhythm
Every cell in the human body has a molecular clock. This molecular clock controls our circadian rhythm through the ebb and flow of cellular production in 24-hour cycles.
This ebb and flow are controlled by transcription factors (proteins that control cellular production) in a genetic circuit that includes the genes CLOCK, BMAL1, Period (Per1, Per2, Per3, often shorthanded collectively as Per), and Cryptochrome .
1) CLOCK and BMAL
Therefore, individuals with low functions of these genes may need less sleep.
The SNP rs1801260 (C) inside of CLOCK is linked to eveningness, being more sleepy during the day, and reduced morningness. People with the T allele are more likely to be morning people and have less total sleep duration [4, 5].
Mice without PGC-1alpha have an abnormal circadian rhythm, body temperature, and metabolic rate .
AhR (Aryl Hydrocarbon Receptor) has important roles in detoxification of certain toxins. In addition, AhR suppresses Per1 production, so it can disrupt CLOCK-BMAL activity and disturb the circadian rhythm . Therefore, it is better to have AhR deactivated most of the time.
Morningness and eveningness are partly heritable. That means you are likely to have a similar type as one of your parents .
Per3 has a variant that lengthens its protein by 18 amino acids. People with the longer form are more likely to be a morning person, whereas those with the shorter form are more likely to be a night owl or have delayed sleep phase syndrome .
People with the longer form also tend to suffer worse from cognitive dysfunction due to sleep deprivation than those with the shorter form .
The longer form seems to increase slow-wave sleep, REM sleep, as well as theta (meditative) and alpha (relaxing) brainwave activities during wakefulness .
The ABCC9 gene is used for making potassium channels mostly in the hearts and skeletal muscles. The A allele of the SNP rs11046205 correlates with reduced sleep duration, but how exactly this gene influences sleep is unclear .
Reducing the function of this gene in fruit flies prevent the flies from sleeping for the first three hours of the night .
Genetics of Insomnia
It’s important to note that just because certain genotypes are associated with a condition or irregular lab marker, it doesn’t necessarily mean that everyone with that genotype will actually develop the condition. Many different factors, including other genetic and environmental factors, can influence the risk of insomnia and other sleep disorders.
1) 5-HT2A Serotonin Receptor
The activation of the 5-HT2A receptor also exhibits a circadian rhythm .
Because stress activates this receptor, people who genetically have higher 5-HT2A activation might be more susceptible to insomnia from stress. Read this post to learn more about 5-HT2A, which might be problematic in people with insomnia.
- rs6311 -1438 G/A: The “T” allele results in more receptors/increased gene expression and more active receptors [26, 27].
- rs6313 102 T/C: The “A” allele is associated with lower general health and social function. The A allele of rs6313 is almost always found together with the T allele of rs6311.
- rs6314 1354 C/T The A allele had reduced ability to activate the receptor or cause downstream signals. This means it causes a blunted signal after activation .
2) Adenosine Receptors
Adenosine is one of the sleep-promoting substances that are present at low levels in the morning and build up throughout the day. At nighttime, high levels of adenosine and strong activation of adenosine receptors are important for quality sleep .
Because caffeine makes you feel awake by blocking adenosine receptors, mutations that reduce adenosine receptor function may correlate with insomnia from caffeine consumption.
3) Uridine (P2Y2) Receptors
Like adenosine, uridine is another sleep-inducing substance. High levels of uridine in the brain and uridine receptor activation at night is important for sleep. Uridine binds to the P2Y receptors in areas of the brain which regulate natural sleep .
BDNF production during the day correlates with the amount of slow-wave (deep) sleep during the subsequent night, suggesting that BDNF is a measure of sleep pressure (the body’s desire to sleep) .
BDNF appears to have a circadian rhythm, being high during the day and lower at night .
People the T allele of the BDNF SNP rs6265, which lower BDNF levels, may not sleep as deeply as people with the C allele or the CC genotype. In addition, the T allele correlates with worse cognitive decline due to sleep deprivation .
5) Calcium Signaling Genes
ROR1 controls the development of neurons together with ROR2. ROR1, ROR2, and PLCB1 are important in learning and memory. The significant SNP (rs11208305) inside of ROR1 gene is associated with insomnia among some female patients .
PCLB1 SNPs were strongly associated in male patients .
Other genes containing insomnia-associated SNPs are :
- CACNA1A (calcium voltage-gated channel subunit alpha 1A), a protein involved in moving calcium between neurons. It appears that rs2302729 affects sleep quality, while rs7304986 affects time laying in bed before falling asleep .
- GNAS (GNAS complex locus) stimulates adenylate cyclase, which converts ATP to cAMP.
- NOS3 (nitric oxide synthase 3), which produces nitric oxide in the blood vessel.
- ADCY8 (adenylate cyclase 8) also breaks down ATP to cAMP .
Increasing calcium and cAMP in the cells may help with this pathway.