This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obstructive sleep apnea (OSA) is a disorder characterized by recurrent episodes of apnea (no airflow) and hypopnea (partially obstructed airflow) which occur during sleep, associated with oxygen desaturation, sleep fragmentation, and with symptoms of disruptive snoring and daytime sleepiness. Its prevalence (defined by an apnea hypopnea index (AHI) greater than 5) in middle-aged adults is 9% in women and 24% in men. A number of risk factors probably interact to increase propensity for repetitive upper airway collapse occurring with sleep. In any person, this is determined by anatomic and neuromuscular factors that influence upper airway size and function. Recognized risk factors are obesity, male gender, small upper airway size, and ventilatory control mechanisms. A major thrust of our work has been to characterize and quantify the role of inheritance in this disorder. Specifically, over the last 10 years, we have assembled a unique cohort of 2200 members of 240 families ascertained through a proband with obstructive sleep apnea (OSA) and 72 families ascertained from the community. Physiological and anatomic measurements have allowed us to describe the fundamental epidemiology and the familial aggregation of OSA. This unique population, the forthcoming availability of a genome-wide scan, as well as our comprehensive analytic resources, ideally position us to address fundamental questions regarding the pathogenesis, including the underlying genetic bases, of OSA and related cardiovascular disease (CVD) phenotypes. We now propose an expanded reassessment of all available subjects for whom we have genome scan and for 200 of our newly recruited minority cohort members (total n=700). The sample will be approximately 50% male, and include 300 Caucasians and 400 African Americans, and 80 subjects age 6-18 years. We will comprehensively characterize the OSA phenotype, applying state-of-the-art technology to quantify obstructive breathing parameters that are more specific measures of upper airway obstruction than the AHI. Subjects also will undergo a biochemical profile and assessment of vascular function, including assessment of novel CVD risk factors that may be related to OSA.
Specific aims are: 1) to investigate new phenotype characterizations of OSA; 2) to determine if the covariation of CVD risk factors and OSA is explained by common genetic effects; 3) to quantify the association between markers of inflammation and oxidative stress with severity of OSA; 4) to identify genes for phenotypes that include: a) OSA, b) putative OSA-metabolic syndrome, and c) novel CVD risk factors; 4) to determine if rate of change in the AHI is predicted by demographic and metabolic factors; and 5) To determine if rate of progression of OSA is determined by a major gene(s). Subjects will be scheduled to first have an in-home sleep study to collect data for longitudinal analyses comparable to those obtained during the previous home visits. All other data will be collected during an overnight stay at the General Clinical Research Center. Procedures in the GCRC will include the following: urine collection - overnight urine will be assayed for albumin, norepinephrine, and creatinine; ankle-arm doppler blood pressure measurement; anthropometry height, weight, neck size, waist measurement, skinfold measurements, bioelectric impedance; electrocardiogram; endothelial function; expired nitric oxide, rhinometry; pulmonary function; questionnaire to describe symptoms, medical history, exposures, nutrient intake, subjective sleepiness, attention testing; and cephalometry.
Showing the most recent 10 out of 753 publications
