Genetics of Sleep and Insomnia – 21 Genes & SNPs to Check

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

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 ].

In addition to the circadian rhythm genes, DEC2 and Per3 are associated with changes in sleep requirements [ 1 ]. 1) CLOCK and BMAL

Deactivating CLOCK and BMAL1 genes decrease total sleep time in animal models [ 2 , 3 ].

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 , 4 ].

The SNP rs2228099 inside of BMAL1 may be associated with insomnia and early awakening among middle-aged women [ 6 ]. 2) PGC-1alpha

PGC-1alpha has important roles in metabolism and mitochondrial health. It also activates clock genes, which control the circadian rhythm [ 7 , 8 ].

Mice without PGC-1alpha have an abnormal circadian rhythm, body temperature, and metabolic rate [ 9 ].

In some individuals, the CC genotype of rs8192678 inside PGC-1alpha is associated with worse insomnia in combination with ApoE4 [ 8 ]. 3) AhR

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 [ 10 ]. Therefore, it is better to have AhR deactivated most of the time.

The SNPs rs2066853 ( AhR , A) and rs2292596 (AhRR, G or GC) are associated with insomnia and early awakening, especially in middle-aged women [ 6 ]. 4) DEC2

DEC2 (encoded by the BHLHE41 gene) represses CLOCK/BMAL1 activity. A mutation in DEC2 is associated with shorter sleep in humans and increased wakefulness in mice [ 11 ]. 5) Per3

Morningness and eveningness are partly heritable. That means you are likely to have a similar type as one of your parents [ 12 ].

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 [ 13 ].

People with the longer form also tend to suffer worse from cognitive dysfunction due to sleep deprivation than those with the shorter form [ 14 ].

The longer form seems to increase slow-wave sleep, REM sleep, as well as theta (meditative) and alpha (relaxing) brainwave activities during wakefulness [ 14 ].

The SNP rs10462021 inside of Per3 is associated with delayed sleep phase syndrome [ 15 ]. 6) ABCC9

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 [ 16 ].

Reducing the function of this gene in fruit flies prevent the flies from sleeping for the first three hours of the night [ 16 ].

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.

Insomnia is partly contributed by genetics; approximately 35% of people with insomnia have some insomniac family members, with the mother being the most commonly affected [ 17 ].

In addition to the circadian rhythm genes, like BMAL, PER3 and CLOCK, there are other genes that may play a role in insomnia [ 18 , 19 , 20 ]. 1) 5-HT2A Serotonin Receptor

Blocking the 5-HT2A receptor promotes sleep in rats. Drugs that block 5-HT2A receptors are under development and clinical trials for the treatment of insomnia in humans [ 21 , 22 ].

The activation of the 5-HT2A receptor also exhibits a circadian rhythm [ 23 ].Activation of this receptor decreases glutathione and BDNF , two substances that are important for quality sleep [ 24 , 25 ].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. Important SNPs 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 [ 28 ]. 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 [ 29 ].Because caffeine makes you feel awake by blocking adenosine receptors, mutations that reduce adenosine receptor function may correlate with insomnia from caffeine consumption.There are four types of adenosine receptors ( A1R , A2aR , […]

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