Genetics of insomnia: Scientists use variant-to-gene mapping to prove gene Pig-Q is associated with sleep regulation

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

Texas A&M geneticist and evolutionary biologist Alex Keene collaborated with Penn’s Allan Pack and Philip Gehrman and CHOP’s Struan Grant on the groundbreaking research, published on Jan. 6 in Science Advances.

“There have been enormous amounts of effort to use human genomic studies to find sleep genes,” Keene said. “Some studies have hundreds of thousands of individuals.  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.”

Keene says the most exciting thing about the team’s work is that they developed a pipeline starting not with a model organism, but with actual human genomics data.

“There is an abundance of human genome-wide association studies (GWAS) that identify genetic variants associated with sleep in humans,” Keene said. “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, which is 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.”