Gene identified in people who need little sleep

Sept. 18, 2019

Healthy sleep involves not only getting enough hours of sleep but sleeping at the right time of day and having good quality sleep. Previous studies have led to the identification of over 50 families with people who need less than six and a half hours of sleep a night to feel well rested.

To better understand why some people need much less sleep than most, a team led by Dr. Ying-Hui Fu and Dr. Louis Ptáček at the University of California, San Francisco carried out a study in a family with three generations of naturally short sleepers to look for genes involved in their unusual sleep patterns.

Results were published online in Neuron.

Using whole exome genome sequencing, the researchers searched for gene mutations that only the naturally short sleepers had. They found a rare mutation in the ADRB1 gene that was being passed through the family. Family members who inherited one copy of this mutant gene had a shortened sleep cycle. The ADRB1 gene codes for the β1-adrenergic receptor. Adrenergic receptors are found on many cells in the body and respond to hormones, including those known to regulate the sleep/wake cycle.

The researchers found that certain brain cells expressed high levels of the β1-adrenergic receptor. These cells were located in a brain region that’s involved in regulating sleep behaviors called the dorsal pons. The brain cells were active when mice were in REM sleep or awake, but not during non-REM sleep.

To learn more about the mutation’s effects in the brain, the researchers created genetically engineered mice with the altered gene. Mice with the genetic mutation slept almost an hour less each day than normal mice. They had about seven minutes less of REM sleep and 53 minutes less of non-REM sleep.

Brain cells with the ADRB1 mutation showed altered activity and electrophysiological properties, making them more easily activated. Mice with the mutation showed increased activity of brain cells with the β1-adrenergic receptor compared with normal mice.

When researchers turned on brain cells with the β1-adrenergic receptor during non-REM sleep using a light-activated protein, the mice woke up. These results suggest that increased activity of wake-promoting brain cells may be one of the mechanisms underlying naturally shorter sleep cycles.

“Natural short sleepers experience better sleep quality and sleep efficiency,” Fu says. “By studying them, we hope to learn what makes for a good night's sleep, so that all of us can be better sleepers leading happier, healthier lives.”

NIH has more information.