Bouncing back after a sleepless night – It’s genetic.

Adenosine is a molecule produced by the body that has a number of functions. You may know it best as part of the cellular energy molecule A/TP – adenosine triphosphate, but it also plays a role in regulating heart rhythm and in sleep.  In the brain, adenosine acts as a neuromodulator that promotes sleep as part of your natural homeostatic sleep drive. The homeostatic sleep drive is the natural buildup of the need for sleep over the course of the day.[ref] [ref] In addition to increasing the drive to sleep, adenosine interacts with BDNF (brain-derived neurotrophic factor) in moderating the length of slow wave sleep cycles.

Adenosine deaminase (ADA) is an enzyme that converts adenosine into inosine, thus regulating the level of adenosine in the body and breaking down adenosine from foods. It is also involved in the immune system, and a complete lack of adenosine deaminase causes severe combined immunodeficiency.

The ADA gene variant rs73598374 (T allele) has been shown in studies to decrease the amount of adenosine deaminase by 20 – 50%, thus leading to an increase in adenosine.[ref] This variant has been shown to increase the amount of slow wave sleep, the deep non-REM sleep. This can be seen on EEG measurements of sleep wave patterns during sleep studies. [ref] One study concludes “The higher EEG spectral power indicates that the sleep of individuals carrying the [T ] allele may be more intense”.*[ref]

The variant doesn’t seem to impact the overall length of sleep or sleep latency all the much during normal sleep conditions. But studies do show that the T-allele increases sleepiness/ fatigue, and makes carriers more error prone the next morning after a period of sleep deprivation as compared to people without the T-allele.[ref][ref]

One study on this ADA variant found that those carrying the T allele had significantly higher salivary amylase levels after disrupted sleep.[ref] Higher amylase levels are used as a measure of stress and increased sympathetic nervous system.[ref]

Check your 23 and Me results for  rs73598374 (v4, v5):

  • T/T: decreased adenosine deaminase, more slow-wave sleep, harder to bounce back after a sleepless night
  • C/T: decreased adenosine deaminase, more slow-wave sleep, harder to bounce back after a sleepless night
  • C/C: normal adenosine deaminase

*Note that when reading through the studies, the orientation is opposite of the way 23andMe reports on this gene. So just remember that A=T and C=G.


The biggest negative effect of the T-allele was seen after sleep deprivation. It seems that this variant keeps you from bouncing back after a night staying up too late. So getting a consistently good nights sleep may be more important for you than others.

Caffeine acts on the adenosine receptor, blocking the receptor to make you feel less sleepy.  Those who carry the rs73598374 T allele may find that caffeine is very effective on morning sleepiness and for reducing errors after a less than perfect night’s sleep.

Alcohol also interacts with the adenosine system. While the occasional drink before bed usually makes people sleepy, chronic alcohol use messes with sleep quality through affecting adenosine.  So it may help to cut down on (or cut out completely) alcohol, especially before bed.

Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.