NHLBI TOPMed: The Cleveland Family Study (CFS)

The Cleveland Family Study (CFS) is one cohort involved in the WGS project. The CFS was designed to provide fundamental epidemiological data on genetic and non-genetic risk factors for sleep disordered breathing (SDB). In brief, the CFS is a family-based study that enrolled a total of 2284 individuals from 361 families between 1990 and 2006. The sample was selected by identifying affected probands who had laboratory diagnosed obstructive sleep apnea. All first degree relatives, spouses and available second degree relatives of affected probands were studied. In addition, during the first 5 study years, neighborhood control families were identified through a neighborhood proband, and his/her spouses and first degree relatives. Each exam, occurring at approximately 4 year intervals, included new enrollment as well as follow up exams for previously enrolled subjects. For the first three visits, data, including an overnight sleep study, were collected in the participants' homes while the last visit occurred in a general clinical research center (GCRC). Phenotypic characterization of the entire cohort included overnight sleep apnea studies, blood pressure, spirometry, anthropometry and questionnaires. The GCRC exam (n=735 selected individuals) included more comprehensive phenotype data on a focused subsample of the larger cohort, to permit linking SDB phenotypes with cardio-metabolic phenotypes, with an interest in identifying genetic loci that are associated with these related phenotypes. In this last round of data collection, a subset of 735 individuals was selected based on expected genetic informativity by choosing pedigrees where siblings had extremes of the apnea hypopnea index (AHI). Participants underwent detailed phenotyping including laboratory polysomnography (PSG), ECG, spirometry, nasal and oral acoustic reflectometry, vigilance testing, and blood and urine collection before and after sleep and after an oral glucose tolerance test. A wide range of biochemical measures of inflammation and metabolism were assayed by a Core Laboratory at the University of Vermont. 994 individuals were sequenced as part of TOPMed Phase 1, including 507 African-Americans and 487 European-Americans. Among the sequenced individuals, 156 were probands with diagnosed sleep apnea, an additional 706 were members of families with probands, and 132 were from neighborhood control families. 298 individuals were sequenced as part of TOPMed Phase 3.5, including 169 African-Americans and 129 European-Americans. Among the newly sequenced individuals, 33 were probands with diagnosed sleep apnea, an additional 214 were members of families with probands, and 51 were from neighborhood control families. Comprehensive phenotypic and pedigree data for study participants are available through dbGaP phs000284. ]]>
TOPMed Whole Genome Sequencing Methods: Freeze 9TOPMed Whole Genome Sequencing Methods: Freeze 10CFS Cohort Study Inclusion Criteria: Cases were probands with laboratory-diagnosed obstructive sleep apnea (AHI > 15 or treated with CPAP). All cases and their first degree and selective second degree relatives and spouses comprised the "case family" sample. Control probands were selected as a neighbor of the case proband. Their first degree relatives and spouses comprised the control family sample. Exclusion criteria for the CFS cohort study: Inability to provide informed consent; no family relationship with cases or controls. Additional exclusion criteria for cases were known congenital disorder associated with sleep apnea. CFS TOPMed Whole-Genome Sequencing Study Inclusion Criteria: We prioritized individuals for participation based on the availability of phenotype data on sleep apnea and availability of DNA.]]>
The Cleveland Family Study contains longitudinal data (multiple observations per person). Exam visits occurred as many as 4 times over a 15 year time interval. New participants joined the study during subsequent waves of data collection, thus data are available from one to four exams per participant. The variable named VISIT denotes the type of visit and are labeled as VISIT #1 (1990-2001), VISIT #2 (1996-2001), VISIT #3 (1999-2001) and VISIT #5 (2001-2005) (there is no VISIT #4). These visits did not occur in "waves", instead they reflect which visit number was recorded. Recruitment was rolling, thus some individuals had a first visit (VISIT = 1) after others had a second or third visit (VISIT = 2 or 3). The first 3 visits occurred in participants' homes. Individuals who participated in visits 2 and 3 included as many participants who were available for examination from a prior visit. There were also additional family members and new minority families recruited later and recorded as visit 1 or 5, depending on type of data collected. Visit 5 occurred in a dedicated clinical research facility (GCRU). This visit targeted minority families and families in whom a prior microsatellite exam had been conducted (selected for genetic informativity). Data collection for visit 5 was more comprehensive - it generally included prior measurements made as well as more detailed biochemical data, ECGs, endothelial function, and sleep staging data. Thus, the data from VISIT = 5 accounts for the most recent visit for data collected on individuals in the Cleveland Family Study and represents the most complete data collection but only includes data for 735 participants. ]]>