Sleep Report: Genetic Causes of Sleep Problems

Below is a quick overview of how your genetic variants impact various aspects of sleep including insomnia, circadian rhythm, and sleep quality.


Insomnia Related Genes:

Gene RS ID Risk Allele YOU Notes about the Risk Allele:
GSK3B rs334558 G Increased risk of insomnia in depression[ref]
PER2 rs7602358 G Increased risk of insomnia, especially when stressed[ref]
GABRA6 rs3219151 T Increased risk of insomnia with adverse life events[ref]


GSK3B gene: The GSK3B gene involves both circadian rhythm and glucose metabolism. This is one gene that is influenced by lithium orotate, which may be a supplement to try in the evening if you don’t have any contraindications for it.

PER2: One of the core circadian clock genes. Concentrate on keeping your circadian rhythm on track with consistent sleep time (even on weekends), blocking blue light from electronics for several hours before bed, and getting sunlight in the morning when you wake up.

GABRA6: GABA is the ‘off’ switch regulating neurotransmission. 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] Ashwagandha is a supplement that may help with regulating cortisol from stress.[ref][ref] (Read more about ashwagandha research) Try a warm cup of tulsi tea before bed. Holy Basil, found in tulsi tea, may also decrease cortisol.[ref]

Turning off the worry at night is tough, but being prepared with something to take your mind off ‘the worry’ can help. For example, keeping your phone by the bed (in the red-shift mode so that it doesn’t wake you up) and having a slightly boring podcast ready to play is one thing that works for some people. A Dateline podcast (Lester Holt’s voice!) or a good history podcast usually works for me. Another option is having relaxing music ready to play, such as the sleep selections from You could also search on YouTube for “delta waves music”.

Genetic variants that impact sleep quality:

Almost as important as the amount of sleep is the quality of your sleep. We all need adequate amounts of deep, slow-wave sleep and REM sleep.

Gene RS ID Risk Allele YOU Notes about the Risk Allele:
ADA rs73598374 T Decreased adenosine deaminase; more slow-wave sleep; groggy in the morning.[ref][ref][ref]
BDNF rs6265 T Decreased BDNF; averages 20 minutes less deep sleep[ref]
CLOCK rs11932595 G Increased risk of  sleep disturbances, sleep difficulty[ref][ref]

Lifehacks for sleep quality genes:

ADA: While this variant is great in that it increases the amount of slow-wave sleep, the trade-off is being groggy without enough sleep.  Be sure that you allow enough time for sleep each night.

BDNF: There are several ways to boost BDNF. Aerobic exercise for at least 30 minutes has been shown to increase BDNF.[ref][ref] Lion’s mane mushroom extract increases BDNF.[ref] Exposure to sunlight also increases BDNF.[ref]

CLOCK: The CLOCK gene is one of the core circadian genes that is important for controlling your whole body’s 24-hour circadian rhythm. CLOCK protein levels rise during the daytime and are repressed at night. Focusing on getting your circadian rhythm in sync via blocking blue light in the evening, going to bed at a consistent time (even on weekends), and getting bright light each morning may help with this variant.

Sleep duration (short sleepers):

Gene RS ID Risk Allele YOU Notes about the Risk Allele:
BHLHE41 rs121912617 C Rare mutation.  Naturally need less sleep (avg. 6 – 6.5 hours/night)[ref]

Lifehacks for short sleep:

BHLHE41: There doesn’t seem to be a significant drawback, as far as health goes, to the reduced amount of sleep for people with this rare mutation. If you are in the 0.5% of people with this mutation, take it as an answer to why you need less sleep.

Circadian rhythm genes that affect sleep timing:

Gene RS ID Risk Allele YOU Notes about the Risk Allele:
CLOCK rs1801260 G Higher activity level in the evening often leading to delayed sleep
PER2 rs35333999 T Likely to stay up later – e.g. evening chronotype; this variant is linked to a longer circadian period
AANAT rs28936679 A Increased risk of Delayed Sleep Phase Disorder (rare)
PER3 rs150812083 G Linked with familial advanced sleep phase disorder[ref]

Lifehacks for circadian rhythm genes:

CLOCK: If you are naturally more active in the evening hours, it can be hard to wind down and get to sleep. Blocking blue light in the evening can help because it allows melatonin levels to rise at the right time. On average, people who carry two copies of the rs1801260 stay up about an hour later each evening than people with the more common genotype. If this is you, one option is to adjust your morning work schedule, if possible, to allow yourself the extra hour of sleep in the morning.

PER2: People with this specific PER2 genotype may be naturally inclined to stay up a bit later in the evening hours. One key here is that it is important to keep bedtime consistent and not let it creep later and later. Sleeping and eating at consistent times both during the week and on weekends is important here.

AANAT: This AANAT rare mutation is linked to Delayed Sleep Phase Disorder.

Melatonin (from tryptophan):

Melatonin levels rise at night when the sun sets and pineal melatonin production stops in the morning with exposure to bright light. Melatonin acts as a signal to reset your circadian rhythm and keep it on track. Additionally, melatonin is essential to many overnight processes your body undergoes while you sleep.

Gene RS ID Risk Allele YOU Notes about the Risk Allele:
TPH2 rs4290270 T Decreased tryptophan conversion, increased early waking and depression
TPH2 rs4570625 G GG only: decreased tryptophan conversion

Lifehacks for melatonin genes:

TPH2: The TPH2 gene codes for an enzyme that converts tryptophan into serotonin and then melatonin. Blue light exposure at night decreases melatonin production. If you have impaired conversion, blocking blue light at night is very important. Additionally, you may want to consider supplementing with low-dose timed-release melatonin, depending on your age.

Histamine and Early Waking Insomnia

In addition to its role in allergies and gastric acid production, histamine also acts in the brain as a neurotransmitter that makes you more alert.[ref]

Histamine levels naturally rise in the morning to make you more alert, but too much histamine or histamine increasing too early could cause early waking insomnia (e.g. waking up at 3:30 am, unable to fall back to sleep).

Gene RS ID Risk Allele YOU Notes about the Risk Allele:
AOC1 rs10156191 T Reduced production of DAO, which is needed to breakdown histamine in the intestines.
AOC1 rs2052129 T
AOC1 rs1049742 T
AOC1 rs1049793 G
HMNT rs1050891 A Reduced breakdown of serum histamine
HMNT i3000469 T

Lifehacks for histamine-related variants:

Consider trying out a low histamine diet to see if it helps your sleep. (Read more about histamine intolerance and low-histamine diets.)

One quick way to test to see if decreasing histamine helps you sleep longer is to take a Benadryl at night. Benadryl blocks the histamine receptors in the brain and also decreases histamine levels a little bit. This is not a good long-term solution…

Caffeine metabolism:

One of the main driving forces of feeling sleepy at night is the accumulation of adenosine in the brain. Caffeine blocks the adenosine receptor, making you feel more alert. Individuals differ quite a bit in their metabolism of caffeine. Fast metabolizers may be able to drink caffeine later in the day, but for slow metabolizers, caffeine after noon may take a big toll on sleep quality.

Gene RS ID Risk Allele YOU Notes about the Risk Allele:
CYP1A2 rs762551 C Slower metabolizer of caffeine[ref]
ADORA2A rs5751876 C CC only: high caffeine intake may make you anxious[ref][ref]

 Lifehacks for caffeine:

Slower caffeine metabolizers who aren’t sleeping well should take a serious look at their caffeine consumption and timing. One thing that many people don’t realize is that caffeine can affect the ability to stay asleep all night. So while you may be able to fall asleep OK after drinking a cup of coffee in the afternoon, it may affect your restlessness and ability to stay asleep later at night.[ref]

Try limiting caffeine to one or two cups of tea or coffee in the morning. Cut yourself off by noon and see if it improves your sleep quality. Yes, this means not drinking iced tea or caffeinated soda with dinner.

Bruxism (Teeth Grinding):

Gene RS ID Risk Allele YOU Notes about the Risk Allele:
HTR2A rs2770304 C increased risk of bruxism (teeth grinding)[ref]
HTR2A rs6313 A increased risk of bruxism[ref][ref]
DRD1 rs686 G GG only: increased risk of bruxism[ref]

Lifehacks for grinding your teeth:

HTR2A is a gene that codes for a serotonin receptor. For some people, SSRIs can cause teeth grinding. Talk with your doctor, if this is the case for you.[ref][ref][ref][ref]

Other lifehacks for bruxism include using a nightguard or trying relaxation methods such as massage or physiotherapy. Trigger point therapy with ‘perfect spot #7‘ may give temporary relief.