Recent cross-sectional studies have demonstrated that obstructive sleep apnea (OSA) is highly prevalent and associated with substantial morbidity. Previous studies have demonstrated familial aggregation for OSA unrelated to environmental factors and have suggested that OSA is a multifactorial disease, influenced by anatomic and physiological factors, with a strong age dependency and with variable expression in men and women. Racial differences in age of onset and underlying risk factors were also suggested. For this study, the data consist of 200 families ascertained through a proband with OSA and 65 families ascertained from the community. These individuals are characterized phenotypically by overnight in-home sleep studies, questionnaires, anthropometry, spirometry, physical examination, blood pressure and cephalometry to assess OSA risk factors and/or intermediate phenotypes. Longitudinal follow-up will be used to define the rate of progression and age dependency of OSA. A nested case control study will be used to address the pathogenic relationship between OSA and hypertension. Variance component modeling will be used in (a) risk factor assessment (demographic data, obesity measures, smoking exposure, anatomic features, lung function measures, etc.); (b) familial aggregation to test the significance of genetic and shared environmental factors, as well as to test for gene-environment interactions; and pleiotropy studies to assess the contribution of pleiotropy to variation in OSA measures. Segregation analysis will be used to examine whether the distribution of apnea measures can be explained by major genetic effects. Future studies should include genotyping families enriched with relatives affected with OSA for linkage analyses.
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