In this genetic-epidemiological study of Obstructive Sleep Apnea (OSA), we propose further investigation of the genetic and etiologic bases for OSA and OSA-associated co-morbidities in a unique, racially diverse family cohort (n= 2200) who have previously undergone overnight sleep studies. Cohort members from structurally informative families for OSA (n=700), most of whom will have had a genome scan performed prior to the study's inception, will undergo additional physiological and biochemical measurements and longitudinal follow-up to derive detailed phenotypic characterization of OSA and related cardiovascular disease (CVD) risk factors and subclinical disease. Newly available technology will be used to quantify specific and sensitive indices of obstructive breathing parameters and sleep fragmentation. These will provide more precise estimates of the OSA phenotype. Subjects also will undergo a biochemical profile and evaluations of vascular function, including assessment of novel CVD risk factors that may be related to OSA based on: i. common genes (e.g., that influence fat distribution); and/or ii. their role as indices of OSA disease severity (e.g., reflecting hypoxic or adrenergic tissue responses). Studies include: In-laboratory determination of sleep-related hypoxemia, arousal, airflow limitation and respiratory effort; b. In-laboratory assessment of biochemical markers, anthropometry, and physiological functions (many measured both in the evening and morning surrounding the sleep study); c. In-home re-assessment of the apnea hypopnea index (AHI), using comparable technology to what was used in the first 10 years of the study. Rigorous analyses, using a variance components-segregation analysis framework, will be used to: i. derive new phenotypes for OSA with estimates of heritability; ii. Assess genetic linkages for these phenotypes; iii. Determine metabolic and vascular responses to OSA-related nocturnal stresses; iv. Model longitudinal changes in the AHI. We will dissect the sharing or non-sharing of the genetic and non-genetic determinants of phenotypes potentially on a causal pathway leading to OSA. Additional longitudinal follow-up of this cohort will identify determinants of OSA progression, the co-variation of OSA with other risk factors, and its natural history. These studies will provide new data that will address the genetics and pathophysiology of OSA and associated traits. Such data are needed to address critical questions regarding the treatment and prevention of a disorder with a huge public health impact related to its high prevalence and associated co-morbidity (CVD, hypertension, sleepiness, impaired quality of life, accidents).