Sleep Disorders and Sleep Deprivation: An Unmet Public

Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem
http://www.nap.edu/catalog/11617.html
BOLSTERING SOMNOLOGY RESEARCH 263
Sleep-Disordered Breathing
Genetic epidemiological studies conducted over the prior decade have
clearly established that sleep-disordered breathing, although a complex trait,
has a strong genetic basis with evidence of oligogenic inheritance (Buxbaum
et al., 2002). Areas of linkage for the apnea-hypopnea index (AHI) appear
to differ by ethnicity (Palmer et al., 2003, 2004). Association and fine mapping
studies have quantified the potential role of several candidate genes in
the pathogenesis of sleep apnea (Gottlieb et al., 2004b; Larkin et al., 2005a),
with results implicating a gene near the APOe4 locus (Larkin et al.,
2005a). There is also evidence that sleep-disordered breathing and obesity,
a major public health problem, are partly linked by pleiotropic genetic
mechanisms (Palmer et al., 2003, 2004). Thus, future studies of the genetics of
sleep-disordered breathing also likely will illuminate the genetic basis
of obesity. Applying advances in genome association methods to population
studies of sleep apnea will be important in discovering genes for this
and related diseases.
Large scale epidemiological studies in the 1990s quantified the prevalence
of OSA in middle aged and elderly populations (Ancoli-Israel et al.,
1991, 1995; Young et al., 1993). More recently, population-based studies
also identified sleep-disordered breathing to be common in American
school-aged children, with an especially high prevalence in African American
children (Rosen et al., 2003). Other studies have identified the predilection
of other groups to sleep apnea. These include commercial drivers
(Howard et al., 2004), whose occupations place them at particular risk for
sleepiness-associated injuries (Gurubhagavatula et al., 2004). Further work
is needed to develop and apply screening approaches for identifying individuals
at high risk for sleep apnea (see technology section). However, in
the case of commercial drivers, a two-stage screening strategy using questionnaires
and simplified tests was shown to be effective (Gurubhagavatula
et al., 2004). Given that commercial drivers with sleep apnea are likely to
be at an increased risk for crashes, occupational screening of this group
may provide an important opportunity to test the model for occupational
screening for sleep disorders.
There is developing evidence that sleep apnea leads to oxidative stress
(Lavie, 2003). This likely results from the cyclical doxygenation-reoxygenation,
akin to ischemia reperfusion, that occurs with apneic events, causing free radial
production and increased levels of inflammatory molecules. C-reactive protein,
a biomarker for cardiovascular disease, may be elevated in OSA. C-reactive
protein declines with treatment with continuous positive airway pressure
(CPAP) (Yokoe et al., 2003). Increasing oxidative stress is not only relevant to
the cardiovascular risk of sleep apnea but also to its effects on neurocognition.
Cyclical intermittent hypoxia leads to oxidative damage of various groups of
Copyright © National Academy of Sciences. All rights reserved.