Problems sleeping? Your genes could hold the solutions

Your genes could play a role in why you aren’t sleeping well. Genes interact with your life – such as stress, caffeine, light coming through your window at night.  Exploring your genes related to sleep disorders may help you fix your sleep problems.

What is sleep and why do we need it?

“Why do we sleep?” turns out to be a more difficult question to answer than you would think.

We are asleep for about a third of our lives. All animals, both big and small, sleep. So you would think that scientists would know exactly why and how sleep works…

Instead, we have almost as many questions about sleep as we have answers.

Let’s look at the definition of sleep from a prominent sleep medicine textbook: “Sleep is a recurring, reversible neuro-behavioral state of relative perceptual disengagement from and unresponsiveness to the environment. Sleep is typically accompanied (in humans) by postural recumbence, behavioral quiescence, and closed eyes.”[ref]

Yep – big words for laying down, closing your eyes, and going to sleep.

The important thing here, though, is what goes on in the brain while you sleep. While your body is inactive (hopefully), your brain is doing some pretty cool and weird stuff while you sleep. Plus, there are different metabolic processes going on in your body while you are asleep.

Why is sleep so important?

While you sleep, your brain consolidates memories — it makes the things that you learned during the day stick in your brain. This has been known for a long time and is something that researchers frequently experiment with.[ref]

Recently, researchers experimented with just decreasing certain stages of sleep and showed that the neuroplastic changes to the brain in learning happen specifically during deep sleep.[ref]

Studies of sleep deprivation show there can be devastating consequences.

  • For most people, sleep deprivation causes a decrease in speed and accuracy in tests for attention, working memory, processing speed, short-term memory, and reasoning.[ref]
  • One-third of accidents in a survey of commercial truck drivers were caused by drowsy driving due to sleep deprivation.[ref]
  • According to the NTSB, going >20 hours without sleep is equivalent to driving legally drunk. And your risk of being in a car crash goes up 3-fold![ref]
  • This pretty much sums up the rest of the effects of sleep deprivation: ‘studies have shown that short sleep duration is associated with an increased incidence of cardiovascular diseases, such as coronary artery disease, hypertension, arrhythmias, diabetes, and obesity, after adjustment for socioeconomic and demographic risk factors and comorbidities.'[ref]

Stages of sleep:

When you sleep, your brain goes through different periods of activity. These are categorized into slow-wave sleep and REM (rapid eye movement) sleep.

Slow-wave sleep can further be broken down into deep sleep and light sleep. About 50% of sleep time (in adults) is light, non-REM sleep.

Most of your deep sleep comes during the early part of the night, while the latter half of the night has much more REM sleep.[ref]

What causes you to feel sleepy?

We feel the need to sleep each night due to two causes:

  • our natural circadian rhythm – and –
  • increased homeostatic sleep drive

The homeostatic sleep drive is what researchers call the build-up over the course of the day for the need to sleep. This is mainly driven by a build-up of adenosine in the brain, which is then cleared out during sleep.

Adenosine is part of the ATP (adenosine triphosphate) molecule used for cellular energy. The ATP molecule stores energy in its bonds and releases energy as the bonds with phosphate are broken. As you use energy over the course of the day, you build up adenosine in the brain.[ref]

Interestingly, caffeine makes you feel more awake by blocking the adenosine receptors, thus making your brain think that not as much adenosine has built up.

The body’s circadian rhythm is the 24-hour built-in molecular clock.  Many different processes in the body occur at different times of the day based on the circadian clock. For example, the enzymes that you produce to break down food are driven by the timing of your normal eating patterns. You may notice that eating dinner several hours later than normal doesn’t always digest as well.

We (all of us humans) are diurnal, which means our circadian rhythm is set up for being up and active during the day and sleeping or inactive in the dark.

Yep, we are flexible, and people can change over to work the night shift. But that change can come with health consequences, more for some than others.

The genes that control the core circadian rhythm can affect sleep quality as well as mood and cognitive function.

Related article: Circadian rhythm genes and mood disorders


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A recent genome-wide analysis of sleep duration, timing, and disturbances found an overlap between sleep quality and the genetic variants associated with sleep disorders. Essentially, people with genetic variants linked with sleep disorders (whether diagnosed or not) were likely to have poor sleep quality. The study used data from 5000+ people wearing sleep trackers, and then it was replicated with another group.[ref]

Morning Grogginess and the ADA gene:

Not clearing out adenosine quickly enough overnight can cause a person to still feel groggy when they wake up in the morning.  A variant of the ADA (adenosine deaminase) gene is associated with a reduced activity causing adenosine to be cleared away less quickly. Variants in the ADA gene are linked with more deep sleep, but the slower clearance of adenosine means that a short night’s sleep leaves the person feeling groggier than normal.

Check your genetic data for rs73598374 (23andMe v4, v5; AncestryDNA)::

  • C/C: typical clearance of adenosine
  • C/T: reduced clearance of adenosine, more deep sleep but may feel sleepy when waking up[ref]
  • T/T: reduce clearance of adenosine, more deep sleep but may feel sleepy when waking up

Members: Your genotype for rs73598374 is .

Insomnia Genes:

GSK3B gene: The GSK3B gene involves both circadian rhythm and glucose metabolism. This is one gene that is influenced by lithium.

Check your genetic data for rs334558 (23andMe v4, v5; AncestryDNA):

  • G/G: increased risk for severe insomnia in depression[ref]
  • A/G: increased risk for severe insomnia in depression
  • A/A: typical

Members: Your genotype for rs334558 is .

PER2 gene: One of the core circadian clock genes, PER2, has links with insomnia.

Check your genetic data for rs7602358 (23andMe v4, AncestryDNA):

  • G/G: increased risk for insomnia (up to 5-fold), especially with stress[ref]
  • G/T: increased risk for insomnia
  • T/T: typical risk for insomnia

Members: Your genotype for rs7602358 is .

TPH2 gene:  Waking up really early and not being able to fall back to sleep is a form of insomnia known as sleep maintenance insomnia.  A variant in the TPH2 gene, which converts tryptophan into serotonin and then melatonin, has been associated with an increased risk of sleep maintenance insomnia.

Check your genetic data for rs4290270 (23andMe v4, AncestryDNA):

  • T/T: increased risk of waking early, increased risk of depression[ref][ref]
  • A/T: probably a slightly increased risk of waking early, depression (this is the most common genotype)
  • A/A: typical

Members: Your genotype for rs4290270 is .

GABRA6 gene: One recent study found low GABA transmission, associated with rs3219151 T allele (most common allele in Caucasian populations), was linked to depression, suicide risk, and insomnia. It is thought the T allele increases plasma cortisol and stress response, and carriers of the T allele who had a recent life stress event were more likely to have problems with stress-related depression and sleep problems.[ref] So how does GABA affect circadian rhythm and sleep? GABA acts within the suprachiasmatic nucleus (region of the brain controlling circadian rhythm) as a key signal in the neuronal circuits. Experiments have shown that GABA can “shift the circadian rhythm of the master clock.”[ref]

Check your genetic data for rs3219151 (23andMe v4, v5; AncestryDNA):

  • T/T: increased risk of depression, insomnia due to adverse life events
  • C/T: increased risk of depression, insomnia due to adverse life events
  • C/C: typical risk of insomnia

Members: Your genotype for rs3219151 is .

Restless Leg Syndrome and Periodic Limb Movement Disorder

Restless Leg Syndrome (RLS) is a fairly common disorder affecting about 10% of the US population. Periodic Limb Movement Disorder -PLMD (also called Periodic Limb Movements In Sleep – PLMS) is often lumped together with RLS in studies. The two often go together with about 80%-90% of RLS suffers also having PLMD.[ref]

About 40% – 60% of people with RLS have a family history of it, suggesting a strong genetic component. People with a family history of RLS tend to get it at a younger age.[ref] In general, RLS is more likely to be found in women, in older people, and in those with iron storage issues.[ref]

People with restless leg syndrome are at an increased risk of psychiatric disorders. One study showed that 37% of people with RLS met the criteria for a psychiatric disorder – compared to only 15% of people without RLS.[ref]

MEIS1 gene: The MEIS1 gene has been studied for restless leg syndrome. MEIS1 encodes a homeobox protein. (Homeobox genes are involved in forming organs and limbs in embryonic development.) There are several MEIS1 SNPs that have links to an increased risk of RLS and PLMD.

Check your genetic data for rs2300478 (23andMe v4, v5; AncestryDNA):

  • G/G: greater than 1.7x risk of RLS, increased sympathovagal balance during N3 sleep stage[ref][ref]
  • G/T: 1.7x risk of RLS
  • T/T: typical risk of RLS

Members: Your genotype for rs2300478 is .

BTBD9 gene:

Check your genetic data for rs3923809 (23andMe v4, v5; AncestryDNA):

  • A/A: approx. 50% with this genotype will have RLS, 1.9x risk of PLMD without RLS, serum ferritin levels decreased 26%[ref]
  • A/G: higher risk of RLS and PLMD, serum ferritin levels decreased 13%
  • G/G: typcial risk of RLS

Members: Your genotype for rs3923809 is .

Check your genetic data for rs9357271 (23andMe v4, v5; AncestryDNA):

  • C/C: lower risk (<0.63) of RLS[ref]
  • C/T: slightly lower risk of RLS
  • T/T: typcial risk of RLS

Members: Your genotype for rs9357271 is .

MAP2K5 gene:

Check your genetic data for rs6494696 (23andMe v4; AncestryDNA):

  • G/G: increased risk of PLMD (most common allele)[ref]
  • C/G: decreased risk of RLS
  • C/C: decreased risk of RLS[ref]

Members: Your genotype for rs6494696 is .

PTPRD gene:

Check your genetic data for rs1975197 (23andMe v4, v5; AncestryDNA):

  • A/A: increased (1.8x) risk of RLS[ref]
  • A/G: increased risk of RLS
  • G/G: typcial risk of RLS

Members: Your genotype for rs1975197 is .

GABA Receptors: A study of patients with restless leg found that GABA receptor variants may affect restless leg syndrome. GABA, the main inhibitory neurotransmitter, keeps the neurons from being overexcited.[ref]

Check your genetic data for rs2229940 (23andMe v4, v5; AncestryDNA):

  • G/G: typical
  • G/T: earlier age of onset for RLS
  • T/T: earlier age of onset for RLS[ref], also, faster motor reaction times[ref]

Members: Your genotype for rs2229940 is .

Narcolepsy Genes:

Narcolepsy, or excessive daytime sleepiness, occurs in about 1 in every 2,000 people in the US and thought of as an autoimmune disease. It is associated with HLA-DRB1*1501 and HLA-DQB1*0602. HLA-DRB1*1501 is highly correlated with rs3135388 and found to influence the risk of several autoimmune diseases including MS, lupus, and narcolepsy. HLA-DQB1*0602 is found in 90% of people who have narcolepsy, but it can’t be determined by a single SNP that I have found.

Check your genetic data for rs3135388 (23andMe v4, v5; AncestryDNA):

  • A/A: (HLA-DRB1*1501) increased risk of narcolepsy, MS[ref]
  • A/G: (one copy of HLA-DRB1*1501) increased risk of narcolepsy
  • G/G: typical risk

Members: Your genotype for rs3135388 is .

Check your genetic data for rs1154155 (23andMe v4, v5; AncestryDNA):

  • G/G: increased risk of narcolepsy (2.5x increased risk)[ref]
  • G/T: increased risk of narcolepsy
  • T/T: typical

Members: Your genotype for rs1154155 is .

Circadian Rhythm Genes:

Our natural circadian clock is run by several core genes that rise and fall over a 24 hour period, setting the rhythm for all of our body’s functions. Sunlight hitting the retina in the morning resets the circadian clock.

Circadian rhythm disruptions have ties to obesity, difficulty in losing weight, diabetes, Parkinson’s, Alzheimer’s, heart disease, and ADHD symptoms.

CLOCK gene: The aptly named CLOCK gene is part of the core molecular circadian clock.

Check your genetic data for rs1801260 (23andMe v4, v5; AncestryDNA):

  • G/G: higher activity levels in the evening, delayed sleep onset.[ref][ref]
  • A/G: somewhat delayed sleep
  • A/A: typical

Members: Your genotype for rs1801260 is .

Check your genetic data for rs11932595 (23andMe v4, v5  AncestryDNA):

  • G/G: increased sleep difficulty, sleep disturbance[ref][ref]
  • A/G: typical sleep
  • A/A: typical

Members: Your genotype for rs11932595 is .

PER2 gene: The PER2 (period 2) gene is part of your core circadian clock.

Check your genetic data for rs35333999 (23andMe v4, AncestryDNA):

  • C/C: typical
  • C/T: likely to stay up later, evening chronotype, longer circadian period
  • T/T: likely to stay up later, evening chronotype, longer circadian period[ref]

Members: Your genotype for rs35333999 is .

AANAT gene: AANAT (arylalkylamine N-acetyltransferase) controls the production of melatonin in the pineal gland. AANAT enzyme activity is high at night and tied to a person’s circadian rhythm. Polymorphisms in AANAT are more common in those with Delayed Sleep Phase Disorder (Japanese Study).

Check your genetic data for rs28936679 (23andMe v4 only):

  • A/G: higher risk of Delayed Sleep Phase Disorder[ref] rare mutation found in less than 1% of the population.
  • G/G: typical

Members: Your genotype for rs28936679 is .


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Related Articles and Genes:

Circadian Rhythms: Genes at the Core of Our Internal Clocks
Circadian rhythms are the natural biological rhythms that shape our biology. Most people know about the master clock in our brain that keeps us on a wake-sleep cycle over 24 hours. This is driven by our master ‘clock’ genes.

Restless Leg and Periodic Limb Movement Disorder: Genetics and Solutions
Twitchy legs, restless sleep…  That urge to move your legs at night or being woken up with your leg moving rhythmically — both take a toll on sleep quality. And good sleep is foundational for overall health and wellbeing.

Genetics and Teeth Grinding (Bruxism)
Bruxism is a condition where you unconsciously clench or grind your teeth. This can occur when sleeping (sleep bruxism) or while you are awake. Bruxism can cause wear on the enamel of the teeth and even cause teeth to crack. Additionally, people with bruxism may have jaw pain, headaches, migraines, or sleep disorders.

How to log in to 23andMe and download raw data
Step-by-step instructions on how to download your raw data from 23andMe


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.