Researchers identify genetic variations linked to oxygen drops during sleep

October 24, 2019

Researchers have identified 57 genetic variations of a gene strongly associated with declines in blood oxygen levels during sleep. Low oxygen levels during sleep are a clinical indicator of the severity of sleep apnea, a disorder that increases the risk of heart disease, dementia, and death. The study, published today in the American Journal of Human Genetics, was funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.

"A person's average blood oxygen levels during sleep are hereditary, and relatively easy to measure," said study author Susan Redline, M.D., senior physician in the Division of Sleep and Circadian Disorders at Brigham and Women's Hospital, and professor at Harvard Medical School. "Studying the genetic basis of this trait can help explain why some people are more susceptible to sleep disordered breathing and its related morbidities."

When we sleep, the oxygen level in our blood drops, due to interruptions in breathing. Lung and sleep disorders tend to decrease those levels further, and dangerously so. But the range of those levels during sleep varies widely between individuals and, researchers suspect, is greatly influenced by genetics.

Despite the key role blood oxygen levels play in health outcomes, the influence of genetics on their variability remains understudied. The current findings contribute to a better understanding, particularly because researchers looked at overnight measurements of oxygen levels. Those provide more variability than daytime levels due to the stresses associated with disordered breathing occurring during sleep.

The researchers analyzed whole genome sequence data from the NHLBI's Trans-Omics for Precision Medicine (TOPMed) program. To strengthen the data, they incorporated results of family-based linkage analysis, a method for mapping genes that carry hereditary traits to their location in the genome. The method uses data from families with several members affected by a particular disorder.

"This study highlights the advantage of using family data in searching for rare variants, which is often missed in genome-wide association studies," said James Kiley, Ph.D., director of the Division of Lung Diseases at NHLBI. "It showed that, when guided by family linkage data, whole genome sequence analysis can identify rare variants that signal disease risks, even with a small sample. In this case, the initial discovery was done with fewer than 500 samples."

The newly identified 57 variants of the DLC1 gene were clearly associated with the fluctuation in oxygen levels during sleep. In fact, they explained almost 1% of the variability in the oxygen levels in European Americans, which is relatively high for complex genetic phenotypes, or traits, that are influenced by myriad variants.

Notably, 51 of the 57 genetic variants "influence and regulate human lung fibroblast cells, a type of cell producing scar tissue in the lungs," said study author Xiaofeng Zhu, Ph.D., professor at the Case Western Reserve University School of Medicine. This is important, he said, because "Mendelian Randomization analysis, a statistical approach for testing causal relationship between an exposure and an outcome, shows a potential causal relationship between how the DLC1 gene modifies fibroblasts cells and the changes in oxygen levels during sleep."

This relationship, Kiley added, suggests that a shared molecular pathway, or a common mechanism, may be influencing a person's susceptibility to the lack of oxygen caused by sleep disordered breathing and other lung illnesses such as emphysema.
-end-
The project was jointly led by Zhu and Redline, who also direct the National Sleep Research Resource, supported by NHLBI.

Study: Sequencing analysis at 8p23 identifies multiple rare variants in DLC1 associated with sleep related oxyhemoglobin saturation level. DOI: 10.1016/j.ajhg.2019.10.002

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit http://www.nhlbi.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIH... Turning Discovery Into Health

NIH/National Heart, Lung and Blood Institute

Related Sleep Articles from Brightsurf:

Size and sleep: New research reveals why little things sleep longer
Using data from humans and other mammals, a team of scientists including researchers from the Santa Fe Institute has developed one of the first quantitative models that explains why sleep times across species and during development decrease as brains get bigger.

Wind turbine noise affects dream sleep and perceived sleep restoration
Wind turbine noise (WTN) influences people's perception of the restorative effects of sleep, and also has a small but significant effect on dream sleep, otherwise known as REM (rapid eye movement) sleep, a study at the University of Gothenburg, Sweden, shows.

To sleep deeply: The brainstem neurons that regulate non-REM sleep
University of Tsukuba researchers identified neurons that promote non-REM sleep in the brainstem in mice.

Chronic opioid therapy can disrupt sleep, increase risk of sleep disorders
Patients and medical providers should be aware that chronic opioid use can interfere with sleep by reducing sleep efficiency and increasing the risk of sleep-disordered breathing, according to a position statement from the American Academy of Sleep Medicine.

'Short sleep' gene prevents memory deficits associated with sleep deprivation
The UCSF scientists who identified the two known human genes that promote 'natural short sleep' -- nightly sleep that lasts just four to six hours but leaves people feeling well-rested -- have now discovered a third, and it's also the first gene that's ever been shown to prevent the memory deficits that normally accompany sleep deprivation.

Short sleep duration and sleep variability blunt weight loss
High sleep variability and short sleep duration are associated with difficulties in losing weight and body fat.

Nurses have an increased risk of sleep disorders and sleep deprivation
According to preliminary results of a new study, there is a high prevalence of insufficient sleep and symptoms of common sleep disorders among medical center nurses.

Common sleep myths compromise good sleep and health
People often say they can get by on five or fewer hours of sleep, that snoring is harmless, and that having a drink helps you to fall asleep.

Sleep tight! Researchers identify the beneficial role of sleep
Why do animals sleep? Why do humans 'waste' a third of their lives sleeping?

Does extra sleep on the weekends repay your sleep debt? No, researchers say
Insufficient sleep and untreated sleep disorders put people at increased risk for metabolic problems, including obesity and diabetes.

Read More: Sleep News and Sleep Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.