Wednesday, February 8, 2023

Scientists identified a new genetic pathway involved in insomnia

A novel insight that could pave the way for new treatments for insomnia and other sleep-related disorders.

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There has been an enormous effort to use human genomic studies to find sleep genes. Some studies have hundreds of thousands of individuals. But validation and testing in animal models are critical to understanding function. 

A new study has achieved that here. Using human genomics, a team of scientists from Texas A&M University, the Perelman School of Medicine at the University of Pennsylvania, and the Children’s Hospital of Philadelphia (CHOP) has identified a new genetic pathway involved in regulating sleep from fruit flies to humans.

The most exciting thing about the study- scientists developed a pipeline starting not with a model organism but with actual human genomics data.

Texas A&M geneticist and evolutionary biologist Alex Keene said, “There is an abundance of human genome-wide association studies (GWAS) that identify genetic variants associated with sleep in humans. However, validating them has been an enormous challenge. Our team used a genomics approach called variant-to-gene mapping to predict the genes impacted by each genetic variant. Then we 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. 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.”

“The team’s next step is to study the role of a common protein modification, GPI-anchor biosynthesis, on sleep regulation. In addition, he notes that the human-to-fruit flies-to-zebrafish pipeline the team developed will allow them to functionally assess sleep not only genes but also other traits commonly studied using human GWAS, including neurodegeneration, aging, and memory.”

Penn’s Philip Gehrman said“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. Moving forward, we will continue to use and study this system to identify more genes regulating sleep, which could point in the direction of new treatments for sleep disorders.”

Journal Reference:

  1. Justin Palermo et al. Variant-to-gene mapping followed by cross-species genetic screening identifies GPI-anchor biosynthesis as a sleep regulator. Science Advances. Paper link
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