American scientists make progress in decoding the genetics of insomnia

Researchers at Texas A&M University, the Perelman School of Medicine at the University of Pennsylvania and the Children’s Hospital of Philadelphia (CHOP), funded by the US National Institutes of Health, have used human genomics to identify a new genetic pathway involved in regulating sleep from fruit flies to humans. This novel discovery, they say, could pave the way for new treatments for insomnia and other sleep-related disorders.

Using a predictive genomics approach called variant-to-gene mapping, Texas A&M biologist Alex Keene and colleagues proved the gene known as Pig-Q is associated with sleep regulation in humans, flies and zebrafish.

Keene collaborated with Penn geneticist Dr. Allan Pack and clinical psychologist Prof. Philip Gehrman and CHOP geneticist Dr. Struan Grant on the groundbreaking research. Their study has just been published in the prestigious journal Science Advances under the title “Variant-to-gene mapping followed by cross-species genetic screening identifies GPI-anchor biosynthesis as a regulator of sleep.”

"We have achieved this here, largely because we each bring a different area of expertise that allowed for this collaboration’s ultimate effectiveness. The most exciting thing about our work is that we developed a pipeline starting not with a model organism, but with actual human genomics data,”

Texas A&M biologist Alex Keene

What was their study?

“Some studies carried out up to now encompassed hundreds of thousands of individuals,” noted Keene, who previously studied fruit flies and Mexican cavefish that have lost both their eyesight and ability to sleep in order to find the genetic basis of what causes human diseases like obesity, diabetes and heart disease.

“But validation and testing in animal models is critical to understanding function. We have achieved this here, largely because we each bring a different area of expertise that allowed for this collaboration’s ultimate effectiveness. The most exciting thing about our work is that we developed a pipeline starting not with a model organism, but with actual human genomics data,” Keene continued.

The team used the genomics mapping approach to predict the genes impacted by each genetic variant. Then they screened the effect of these genes in fruit flies. “Our studies found that mutations in the gene Pig-Q required for the biosynthesis of a modifier of protein function increased sleep,” said Keene. “We then tested this in a vertebrate model – zebrafish – and found a similar effect. Therefore, in humans, flies and zebrafish, Pig-Q is associated with sleep regulation.”

Their next step is to study the role of a common protein modification, GPI-anchor biosynthesis, on sleep regulation; the human-to-fruit flies-to-zebrafish pipeline they developed will allow them to functionally assess not only sleep genes but also other traits commonly studied using human GWAS, including neurodegeneration, aging and memory.

“Understanding how genes regulate sleep and the role of this pathway in sleep regulation can help unlock future findings on sleep and sleep disorders, such as insomnia,” said Gehrman. “Moving forward, we will continue to use and study this system to identify more genes regulating sleep that could point in the direction of new treatments for sleep disorders.”