Scientists are making progress in deciphering the insomnia gene

A study funded by the National Institutes of Health, involving researchers from Texas A&M University, the Perelman School of Medicine at the University of Pennsylvania, and the Children's Hospital of Philadelphia (CHOP), used human genomics to identify a new genetic pathway involved in sleep regulation from fruit flies to humans, a novel insight that could pave the way
for new treatments for insomnia and other sleep-related disorders.

Alex Keene, a geneticist and evolutionary biologist at Texas A&M University, collaborated with Allan Pack of the University of Pennsylvania, Philip Gehrman, and SCHOP's Struan Grant on the groundbreaking study, published in the journal Science Advances
.

Keene said: "Using human genome research to find sleep genes has gone into a huge effort
.
Some studies have involved hundreds of thousands of people
.
But validation and testing in animal models is critical
to understanding function.
We have achieved this here in large part because each of us brings expertise in different fields to the end result
of this collaboration.
”

Keene says the most exciting thing about the team's work is that they developed a pipeline that starts not with model organisms, but with actual human genomic data
.

Keene said: "There are a large number of human genome-wide association studies (GWAS) that have identified genetic variants
associated with sleep in humans.
However, validating them has been a huge challenge
.
Our team used a genomics method called variant-to-gene mapping to predict the genes
affected by each genetic variation.
We then screened for the effects
of these genes on fruit flies.

"Our study found that mutations in the Pig-Q gene, which are necessary for the biosynthesis of protein function regulators, can increase sleep
.
We then tested it on a vertebrate model zebrafish and found a similar effect
.
Thus, in humans, fruit flies, and zebrafish, Pig-Q is implicated
in sleep regulation.
”

Keene said the team's next step is to investigate the role
of a common protein modification — GPI anchor biosynthesis — in sleep regulation.
In addition, he noted that the human-fruit fly-zebrafish pipeline developed by the team can functionally assess not only sleep genes, but also other features studied using human GWAS, including neurodegeneration, aging, and memory
.

Gehrman, an associate professor of clinical psychology in psychiatry at the University of Pennsylvania and a clinical psychologist at the University of Pennsylvania's Institute of Chronobiology and Sleep, said: "Understanding how genes regulate sleep, and the role of this pathway in sleep regulation, could help unlock future discoveries
about sleep and sleep disorders such as insomnia.
" Going forward, we will continue to use and study this system to identify more genes that regulate sleep, which could point the way
to new approaches to treating sleep disorders.
" ”

Keene's research in his biological clock research center affiliated laboratory is at the intersection of evolution and neuroscience, focusing on understanding the neural mechanisms and evolutionary basis of sleep, memory formation and other behavioral functions in fruit fly and fish models
.
Specifically, he studied fruit flies (Drosophila melanogaster) and Mexican cavefish that lose sight and sleep, with the aim of identifying the genetic basis
of behavioral selection that causes human diseases, including obesity, diabetes, and heart disease.