Researchers from Brigham and Women's Hospital (BWH) and CWRU School of Medicine/Rainbow Babies and Children's (RB&C) Hospital are the first to complete a whole-genome scan for obstructive sleep apnea and obesity.

Their data has identified genes that may help uncover which individuals are predisposed to snoring and provide further evidence that obesity is a major genetic contributor to the condition. These findings will be published in the February 2003 issue of the American Journal of Human Genetics.

"By taking our research to the most basic, genetic level, we were able to examine how sleep apnea and obesity may be linked," said lead author Lyle Palmer, of BWH. "We discovered that there may be a common causal pathway in which several genes work in tandem, elevating risk for both conditions."

"Our data provide intriguing clues that genes which predispose to metabolic abnormalities-for example diabetes-may also increase risk for sleep apnea and obesity, and these genetic associations may provide one explanation for why patients with sleep apnea often suffer from poor health," said Susan Redline, principal investigator on the study and professor of pediatrics at CWRU and RB&C.

Obstructive sleep apnea-a condition commonly characterized by disruptive snoring and daytime sleepiness-affects up to 4 percent of adults. The condition is a risk factor for high blood pressure, heart disease, diabetes and poor quality of life. While the syndrome's most characteristic feature is obesity, the nature of the relationship between body mass index and snoring remains unclear.

In this study, researchers from BWH, Harvard Medical School (HMS), CWRU and RB&C hope to better explain the common ties between the two conditions.

Over a 12-year period, the National Heart Lung and Blood Institute (NHLBI) supported the development of a cohort of greater than 350 families (more than 2,500 individuals) from the greater Cleveland area, most with a member with sleep apnea. Families were followed by Redline and her colleagues at CWRU/RB&C. They monitored performance of sleep, took physical measurements and made other health assessments. Three hundred forty-nine (349) individuals from a sample of the most informative families were genotyped by the NHLBI's Marshfield Center for Mamalian Genetics.

The genome scans revealed that there was a particular genetic area-one involved in metabolic processes-that showed a significant association with both sleep apnea and body weight. This finding suggests that there may be one or more genes relevant to both functions, possibly influencing metabolic rate and breathing control.

Considering the severity of the obesity pandemic in the United States, the research team believes this genetic discovery may begin to answer an increasingly popular question: What genes impact a person's chances of becoming overweight? Further, the team suggests that this question also should be expanded to ask what genes impact a person's chances of becoming overweight and snoring. Importantly, the study also reveals that obesity's toll, even at a genetic level, greatly influences one of the most basic quality of life indicators-sleep.

"Because sleep apnea may also contribute to fatigue, the result is a viscous cycle," said Palmer, also of HMS and CWRU. "If there are genes that predispose individuals to both snoring and obesity, these people may suffer from sleep deprivation and be less physically active. With less activity, weight gain is more likely, thus leading to more severe snoring."

With a clearer understanding of the genetic causes behind both sleep apnea and obesity, in the future clinicians may be better equipped to direct more appropriate therapies.

"Certainly, this emphasizes the need to consider sleep apnea as a possible complicating condition when approaching obese patients," Palmer said.

With a recent grant from the NHLBI, Redline and her colleagues are continuing to study individuals from affected families with detailed assessments of other metabolic parameters collected from overnight sleep studies at the General Clinical Research Center at University Hospitals of Cleveland.

"The newer data will allow us to look in more detail on how obesity, sleep disorders, high blood pressure and diabetes may be related and which genes may predispose to several of these health conditions," said Redline.

Data collected for this study are from the Cleveland Family Sleep Cohort, the largest cohort ever assembled to study the genetics of sleep apnea and related traits. Redline and her team began by studying families in their homes in 1990 and have repeatedly visited them up to three times over 12 years (for a total greater than 2,500 people) and are now funded through 2006. They are studying a sample very intensively, with state-of-the-art blood tests for measures of inflammation, metabolic disturbances (pre-diabetes), vascular measures and body fat composition. They hope to further unravel how sleep disorders interact with other cardiovascular risk factors to increase the risk of developing high blood pressure and heart disease.

Redline is also principal investigator for a number of other NIH-funded studies, including the Sleep Heart Health Study (a multi-center study of more than 6,000 individuals) that has definitively established links between sleep apnea, high blood pressure, heart disease and diabetes; the Cleveland Children's Sleep and Heath Study, a study of 907 children in the greater Cleveland area that has identified childhood risk factors for sleep apnea; the Honolulu Asian American Aging Sleep Study, which is studying the association of sleep disorders with dementia; and the Study of Osteoporetic Fractures Sleep Study, which is assessing risk of falls and fractures in older women with sleep disorders.