Everyone at some point knows the pain of a sleepless night. For some, though, this is an all too frequent occurrence.
A few quick facts:
- 10% of adults (and 22% of the elderly) have insomnia disorder[ref]
- Heritability estimates from twin studies show that insomnia is around 50% genetic; genes lending susceptibility along with environmental factors. [ref] Another study broke this down further, finding that most genetic influence is on the type of insomnia where people have a hard time staying asleep, rather than difficulty falling asleep. [ref]
- 80-90% of people with major depression experience insomnia of some sort, with about half of them experiencing severe insomnia. [ref]
- Insomnia can be either a problem with initially falling asleep or with waking up in the early morning hours and not being able to fall back to sleep.
Is there an “Insomnia Gene”? well, no…
While twin studies and other heritability studies point to genetic variants playing a role in insomnia, there doesn’t seem to be one gene that causes people to get insomnia. It is more complex than that (of course), and studies point to several different genetic variants that perhaps combine with environmental factors (light, diet, stress) to cause those sleepless nights.
Below are a few of the genetic variants (covered by 23andMe data) that have been linked to insomnia. This is just a partial picture, though, and more studies are coming out on the topic all the time.
GSK3B is a gene associated with both circadian rhythm and mood disorders. A variant of GSK3B, rs334558 (G allele, v4 v5) has been associated in a recent study with an almost doubled risk of severe insomnia in depressed patients. These patients also had a greater insomnia response to antidepressant therapy. [ref] Note that this gene is also acted on by lithium, affecting bipolar disorder.
Check your 23andMe results for rs334558 (v4, v5):
- G/G: increased risk of severe insomnia in depression
- A/G: increased risk of severe insomnia in depression
- A/A: normal insomnia risk
The CLOCK gene variant known as 3111T/C (rs1801260) has been fairly well studied. The G allele* is found in about 23% of the population and is associated in many studies with being more active in the evening. Studies have shown that people who carry the G allele of CLOCK rs1801260 may have dampened amplitudes of circadian rhythm functions such as decreased body temperature function and a less stable circadian pattern. [ref] This may lead you to think that the G allele would be associated with insomnia, but this is not necessarily the case…
A study of women (post-menopausal) who had insomnia found that those carrying the CLOCK gene variant (3111T/C) A/A genotype* had higher melatonin levels in the early morning and lower nighttime melatonin levels, the opposite of what it should be… A/A is the most common genotype, so another way of looking at this is that the G allele is protective against insomnia. [ref] Another recent study of Caucasian women also found that the A/A genotype is more frequent in people with insomnia. (*plus orientation to correspond to 23andMe data)
Check your 23andMe results for rs1801260 (v4, v5):
- G/G: decreased risk of insomnia in women
- A/G: decreased risk of insomnia in women
- A/A: normal insomnia risk
One recent study found that 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 that 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 23andMe results for rs3219151 (v4, v5):
- 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: normal risk of insomnia
Basic sleep hygiene techniques are the first place to start. Be sure to:
- sleep in a cool room
- keep it dark at night
- no electronics before bed
- consistent bedtime routine
If you are rolling your eyes, thinking that you have done all that with no results, read on…
Here are some suggestions based on studies that fit with the above genetic causes:
Block blue light at night for CLOCK gene variants:
If you aren’t already wearing blue-blocking glasses, get a pair and wear them every evening for a couple of hours before bedtime. Be consistent and give it a good week or two. A study of insomnia patients in a controlled clinical cross-over trial found that blue-blocking glasses worn for 2 hours before bed for seven days increased total sleep time, overall quality, and soundness of sleep. [ref]
Ensure Vitamin A sufficiency:
Several studies have found that vitamin A deficiency changes (and dampens) circadian rhythms. So ensure that you are getting enough vitamin A in your diet. Check your genes to see whether beta-carotene is a good option for you or if you are better off getting Vitamin A from animal sources.[ref] [ref] Be sure to also get adequate sunlight for vitamin D if you are taking a vitamin A supplement. [ref]
GABA and reaction to stress:
A clinical trial for mindfulness meditation found that it reduced the ‘total wake time’ by 43 minutes on average. [ref]
GABA can be taken as a supplement for sleep… I say that with trepidation because I don’t know how well taking GABA supplements really works as far as crossing the blood-brain barrier. Here is a good article on GABA for sleep from The Sleep Doctor. Passionflower extract has been shown to act on GABA receptors. [ref]
GSK3B and CLOCK:
Look at the supplements you are taking to see if they could be disrupting your sleep. Supplements such as lithium orotate (a GSK3B inhibitor which affects the PER circadian rhythm gene) may affect your circadian rhythm. Try varying the time of day that you take supplements to see if it has an effect. Creatine may also affect sleep for some people. Resveratrol also affects circadian rhythm.
If you are dealing with histamine intolerance symptoms, this could also be playing a role in waking up at 3am… There is a circadian rhythm to mast cell activation and histamine levels can peak in the early morning hours. High histamine may increase your alertness. (This is also why Benadryl, an anti-histamine, makes you sleepy…)