Genetics of Sleep Disturbances

Sleep DisordersA good night’s sleep is invaluable, and many know the frustration of not being able to regularly sleep well.  There are many factors involved in sleeping well, and genetics plays a role in some sleep disorders.  Looking at the genetic basis of your sleep disorder may give you ideas on which path to take to fix the problem.


Circadian Rhythm

One of the first genes that I learned about when I started looked at genetics was the CLOCK (circadian locomotor output cycles kaput) gene.  I found it fascinating that some people really are genetically ‘night owls’.   Circadian rhythm disruptions have been tied to obesity, difficulty in loosing weight, and ADHD symptoms.

Clock gene

Check your 23andMe results for rs1801260:

  • GG: higher activity levels in the evening, delayed sleep onset. [ref][ref]
  • AG: somewhat delayed sleep
  • AA: normal


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 persons circadian rhythm.  Polymorphisms in AANAT are more common in those with Delayed Sleep Phase Disorder (Japanese Study).[ref]

Check your 23andMe results for rs28936679:

  • AG: higher risk of Delayed Sleep Phase Disorder (Japanese)
  • GG: normal

PER3 gene

There are several SNPs and repeats in the PER3 gene that are connected to Delayed Sleep Phase Disorder, but the data isn’t available for 23andMe users.


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]

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

Check your 23andMe results for rs2300478:

  • GG: greater than 1.7x risk of RLS
  • GT: 1.7x risk of RLS
  • TT: normal risk of RLS

BTBD9 gene

Check your 23andMe results for rs3923809:

  • AA: approx. 50% with this genotype will have RLS, 1.9x risk of PLMD without RLS, serum ferritin levels decreased  26%  [ref]
  • AG: higher risk of RLS and PLMD, serum ferritin levels decreased 13%
  • GG: normal risk of RLS


Check your 23andMe results for rs9357271:

  • CC: lower risk (<0.63) of RLS  [ref]
  • CT: slightly lower risk of RLS
  • TT: normal risk of RLS

PTPRD gene


Check your 23andMe results for rs1975197:

  • AA: increased (1.8x) risk of RLS  [ref]
  • AG: increased risk of RLS
  • GG: normal risk of RLS


There are several other SNPs that have been studied in relation to RLS/PLMD that are not included in 23andMe data, as well as several that slightly reduce the risk of RLS.  If either RLS or PLMD is a problem for you, searching through the PubMed studies would be a good idea.


Narcolepsy, or excessive daytime sleepiness, is found in about 1 in every 2,000 people in the US.  It is now thought to be an autoimmune disease and 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 23andMe results for rs3135388 (HLA-DRB1*1501):

  • AA: increased risk of narcolepsy, MS  [ref]
  • AG: increased risk of narcolepsy
  • GG: normal risk


Check your 23andMe results for rs1154155:

  • GG: increased risk of narcolepsy (2.5x increased risk) [ref]
  • GT: increased risk of narcolepsy
  • TT: normal



More to read:

Circadian Rhythms: Of Owls, Larks, and Alarm Clocks

Narcolepsy, the Sleep Disorder, Linked to Immune System Problem

Leave a Reply

Your email address will not be published. Required fields are marked *