Lung Diseases Clinical Trial
To determine intermediate traits for sleep apnea in a case-control study.
BACKGROUND:
Sleep apnea is a common condition that affects 4 percent of middle-aged males and 2 percent
of middle-aged females. There is recent evidence that there is a genetic influence because
first degree relatives of patients with this disorder have an increased risk of having
obstructive sleep apnea. The basis for this increased familial risk is undefined. The
investigators postulated that there were three specific intermediate traits, each of which
reduced upper airway size, thereby increasing the risk of sleep apnea. These intermediate
traits included: a) particular distribution of fat in the neck; b) craniofacial structure;
and c) size of critical soft tissues in the airway (soft palate, tongue, lateral pharyngeal
walls). All of these risk factors could be assessed quantitatively using advanced magnetic
resonance imaging and novel volumetric image analysis techniques that had been developed..
The study was one project within a Specialized Center of Research in Neurobiology of Sleep
and Sleep Apnea.
DESIGN NARRATIVE:
The case-control study identified the structural risk factors for sleep apnea. The study was
complemented by studies in siblings of the patients and controls in order to identify those
traits that demonstrated family aggregation not explained by shared environmental factors.
The investigators believed that these structural risk factors would interact to increase the
risk of sleep apnea. The elucidation of upper airway structural risk factors should provide
the basis for developing new, more effective techniques for screening patients for sleep
apnea and provide the basis for performing future DNA analyses aimed at identifying the
genetic loci for these risk factors.
The specific aims were: 1) to quantify upper airway craniofacial structure, soft tissues and
regional fat deposition using three dimensional magnetic resonance imaging in order to
determine the intermediate traits associated with obstructive sleep apnea utilizing a case
control design in normals and apneics; and 2) to determine the upper airway structural risk
factors for sleep apnea that demonstrated family aggregation and were most likely to have a
genetic component by comparing probands, siblings of probands, neighborhood controls and
siblings of neighborhood controls. The resources included an extensive clinical sleep
practice, sophisticated NM imaging techniques, novel volumetric computer graphics image
analysis and expertise in molecular epidemiology, craniofacial structure, and the genetics
of obesity.
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