How much do our genes contribute to our risk of developing insomnia?
If insomnia affects you, there is a good chance that members of your extended family will have experienced it as well.
In fact, the chance is at least 30 percent, according to a recent article in the journal Nature Reviews Disease Primers.
“Insomnia tends to aggregate in families,” explain the authors.
A 2015 study by Mackenzie J. Lind, from the Virginia Institute for Psychiatric and Behavioral Genetics at Virginia Commonwealth University School of Medicine in Richmond, and colleagues estimated the heritability of insomnia to be around 59 percent in women and 38 percent in men when comparing insomnia symptoms in identical and nonidentical twins.
Speaking about her work to Medical News Today, Lind explained: “The amount of interest and research into the genetics of insomnia has definitely increased in recent years. However, […] twin and family studies examining the heritability of insomnia and related phenotypes have been published since the 1960s.”
So, which genes are to blame?
Finding insomnia genes
It makes sense to start with genes known to play a role in sleep, since insomnia is characterized by difficulties falling or staying asleep.
There is some evidence to suggest that the obvious culprits — namely, circadian rhythm genes and neurotransmitters involved in the regulation of sleep — play a role in insomnia. Yet Lind and others point out that there is a lack of robust and reproducible evidence for many of these candidate genes.
Over the past 2 years, MNT have reported on a couple of studies that used a different approach to identify candidate genes or genetic regions. Genome-wide association studies (GWAS) scan vast amounts of genetic code to find locations with ties to particular traits.
These studies identified a number of novel candidate genes and genetic regions, including some specific to women and some that were specific to men.
The story got a lot more complex last week, when two new studies appeared in the journal Nature Genetics. Both dug deep into the human genome to identify additional regions of the genetic code with links to insomnia.
From genes to brain regions
In the largest GWAS of insomnia to date, the researchers analyzed data from 1,331,010 people and found 956 genes across 202 locations in the genome with a link to insomnia.
Some of these genes were enriched in cortical areas and the striatum in the brain, particularly in a type of cell called medium spiny neurons, which are implicated in reward processing. There was also a link to pyramidal neurons in the claustrum, which is important for the processing of incoming stimuli.
The second study identified 57 genetic locations with links to insomnia.
The results point to increased expression of 135 genes in the cerebellum, frontal cortex, anterior cingulate cortex, hypothalamus, basal ganglia, amygdala, and hippocampus.
The researchers also found an association with a type of cellular process called ubiquitin-mediated proteolysis. This is a mechanism that targets proteins for destruction within cells, and scientists have previously linked it to insomnia.
Research is clearly making headway in identifying those genes that contribute to the genetic risk of developing insomnia — but the heritability is not 100 percent. What else is involved?
Stress also affects our genes
When asked which other factors might contribute to a person’s risk of insomnia, Lind explained that environmental factors — particularly stress — are to blame.
While we generally accept the connection between stress and insomnia, what actually happens in the brain is less clear.
There is plenty of evidence to suggest that our environment — particularly stressful life events — can change which genes are expressed in our cells without directly altering our genetic code. This phenomenon is called epigenetics.
Importantly, epigenetic changes can be passed from parents to children, but they are also thought to be reversible. Researchers have begun to uncover epigenetic influences on how our bodies regulate sleep and respond to stress.
The bottom line is that insomnia has a significant genetic component. Scientists have now identified hundreds of genetic locations that may each contribute a little bit to a person’s overall risk of developing insomnia. Environmental influences can further shape how these genes are expressed, linking life events to insomnia before and after we are born.