Two massive genetic studies home in on the origins of insomnia
Two massive new studies have homed in on the genetic foundations ofinsomnia. The rigorous analyses reveal novel links between insomnia andcertain brain regions, while paving the way for personalizedtreatments.
Insomnia may feel like a purely psychological condition, aside-effect of depression, anxiety or stress. However, an interestingbody of research is beginning to suggest the condition may befundamentally underpinned by genetic triggers.
The first new study, led by the University of Exeter MedicalSchool and Massachusetts General Hospital, looked at UK Biobank datafrom nearly half a million people. The research uncovered 57 geneticregions that could be linked to insomnia. These targeted geneticregions interestingly shared associations with various conditions,particularly of note was a possible causal connection betweeninsomnia and coronary artery disease.
"All of these identified regions are possible new therapeutictargets for insomnia, and 16 of these regions contain known drugtargets," explains Jacqueline Lane, one of the scientists fromMassachusetts General Hospital working on the project. "As well,the new causal relationships indicate the potential usefulness ofinsomnia therapeutics as possible treatments for coronary arterydisease and depression."
The second study examined an even larger dataset, bringingtogether sleep and DNA data from over 1.3 million people. This studyrevealed 202 genetic regions associated with insomnia, covering 956specific genes.
The researchers then investigated which brain cell types andregions utilized these genes, in the hope of better understandingwhat mechanisms underpin insomnia. As well as finding specific celltypes, 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 otherneuropsychiatric disorders, is influenced by hundreds of genes, eachof small effect," says Danielle Posthuma, from VU Amsterdam. "Thesegenes by themselves are not that interesting to look at. What countsis their combined effect on the risk of insomnia. We investigatedthat with a new method, which enabled us to identify specific typesof brain cells, like the so-called medium spiny neurons."
Perhaps the most interesting finding from the second study was thelack of genetic overlap between insomnia and other sleep-relatedtraits. It seems the genetic underpinning of insomnia is more relatedto psychiatric conditions such as depression and anxiety. Thiscompelling discovery suggests prior work investigating insomniatreatments that target sleep-regulating brain areas may have beenlooking in the wrong place.
"A very important finding, because we have always searched forcauses of insomnia in the brain circuits that regulate sleep," saysEus Van Someren, from the Netherlands Institute for Neuroscience. "Wehave to shift our attention to the circuits that regulate emotion,stress and tension. Our first results in that direction are alreadyspectacular."
Realistically, it will be some years before this kind of work isactively translated into a new clinical treatment. The large varietyof different genes that seem to be associated with insomnia mean aneffective treatment isn't as simple as just targeting a singlegene. In the short term though, these studies certainly solidifychronic insomnia as a real and tangible disorder, and not merely aside effect of maybe a stress-related disturbance.
"This study is an immense step forward in understanding thegenetic background of insomnia," says Vladimir Vacic, a scientistfrom 23andMe working on the second study. "The findings underlinethat insomnia is a serious condition, because of the shared geneticrisk of psychiatric disorders metabolic disturbances involved inobesity and diabetes."