Insomnia, Sleepless Nights, and Your Genes

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 lend 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.

Table of Contents

Is there an “Insomnia Gene”? well, no… not specifically.

While twin studies point to genetic variants playing a role in insomnia, there isn’t one gene that causes people to get insomnia. It is more complex than that (of course), and there are several different genetic variants that perhaps combine with environmental factors (light, diet, stress) to cause those sleepless nights.

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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 gene:

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 genetic data for rs334558 (23andMe 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

Members: Your genotype for rs334558 is —.

PER2 gene:

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 —.

CLOCK Gene:

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 genetic data for rs1801260 (23andMe v4, v5):

G/G: decreased risk of insomnia in women
A/G: decreased risk of insomnia in women
A/A: normal insomnia risk

Members: Your genotype for rs1801260 is —.

GABRA6 gene:

One recent study found that low GABA transmission, associated with the 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 genetic data for rs3219151 (23andMe 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

Members: Your genotype for rs3219151 is —.

Lifehacks:

Basic sleep techniques are the first place to start. Seriously – get all of these in place before resorting to drugs, etc.

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