Two massive new studies have homed in on the genetic foundations of insomnia. The rigorous analyses reveal novel links between insomnia and certain brain regions, while paving the way for personalized treatments.

Insomnia may feel like a purely psychological condition, a side-effect of depression, anxiety or stress. However, an interesting body of research is beginning to suggest the condition may be fundamentally underpinned by genetic triggers.

The first new study, led by the University of Exeter Medical School and Massachusetts General Hospital, looked at UK Biobank data from nearly half a million people. The research uncovered 57 genetic regions that could be linked to insomnia. These targeted genetic regions interestingly shared associations with various conditions, particularly of note was a possible causal connection between insomnia and coronary artery disease.

“All of these identified regions are possible new therapeutic targets for insomnia, and 16 of these regions contain known drug targets,” explains Jacqueline Lane, one of the scientists from Massachusetts General Hospital working on the project. “As well, the new causal relationships indicate the potential usefulness of insomnia therapeutics as possible treatments for coronary artery disease and depression.”

The second study examined an even larger dataset, bringing together sleep and DNA data from over 1.3 million people. This study revealed 202 genetic regions associated with insomnia, covering 956 specific genes.

The researchers then investigated which brain cell types and regions utilized these genes, in the hope of better understanding what mechanisms underpin insomnia. As well as finding specific cell types, such as hypothalamic and claustrum neurons, the study also found significant activity of the insomnia risk genes in the brain’s frontal cortex and the subcortical nuclei.

“Our study shows that insomnia, like so many other neuropsychiatric disorders, is influenced by hundreds of genes, each of small effect,” says Danielle Posthuma, from VU Amsterdam. “These genes by themselves are not that interesting to look at. What counts is their combined effect on the risk of insomnia. We investigated that with a new method, which enabled us to identify specific types of brain cells, like the so-called medium spiny neurons.”

Perhaps the most interesting finding from the second study was the lack of genetic overlap between insomnia and other sleep-related traits. It seems the genetic underpinning of insomnia is more related to psychiatric conditions such as depression and anxiety. This compelling discovery suggests prior work investigating insomnia treatments that target sleep-regulating brain areas may have been looking in the wrong place.

“A very important finding, because we have always searched for causes of insomnia in the brain circuits that regulate sleep,” says Eus Van Someren, from the Netherlands Institute for Neuroscience. “We have to shift our attention to the circuits that regulate emotion, stress and tension. Our first results in that direction are already spectacular.”

Realistically, it will be some years before this kind of work is actively translated into a new clinical treatment. The large variety of different genes that seem to be associated with insomnia mean an effective treatment isn’t as simple as just targeting a single gene. In the short term though, these studies certainly solidify chronic insomnia as a real and tangible disorder, and not merely a side effect of maybe a stress-related disturbance.

“This study is an immense step forward in understanding the genetic background of insomnia,” says Vladimir Vacic, a scientist from 23andMe working on the second study. “The findings underline that insomnia is a serious condition, because of the shared genetic risk of psychiatric disorders metabolic disturbances involved in obesity and diabetes.”

The two new insomnia studies were published in the journal Nature Genetics.

Source: University of Exeter / VU Amsterdam

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