Cardiovascular Diseases Clinical Trial
To determine the role of genetic factors influencing risk factors for cardiovascular disease, ultimately identifying specific genes influencing the age-related progression of cardiovascular disease risks.
BACKGROUND:
Understanding the genetic basis of common multifactorial diseases such as cardiovascular
disease (CVD) remains an elusive goal, but the great advances in molecular genetic
technology, statistical genetic methods, and phenotypic assessment of CVD risk factors in
recent years have facilitated more sophisticated genetic studies of risks for heart disease.
The study is a follow-up to one conducted in the 1970's and 1980's. The availability of 5
large kindreds first identified and recruited as part of the "High Blood Pressure in the
Young" program is an important resource. The investigators have an extensive array of
baseline data that was collected in the late 1970s and early 1980s on 750 participants
stemming from that project, although some data are available only on a subset of
participants. The present study population centers on 764 individuals in five large,
multigenerational, extended families (four white and one African-American) originally
examined 25 years ago. Data collected from the original participants include hundreds of
biochemical, medical, physiological, behavioral, physical, psychological, genetic and
demographic traits.
DESIGN NARRATIVE:
The study consists of four specific aims: 1) Collect 25-year follow-up data from
approximately 500 of the original participants, and new data from approximately 500 of their
relatives not examined in the original study. The cardiovascular disease risk factor
phenotypes to be collected include hemodynamic measures, carotid intima-media thickness, and
measures of cardiopulmonary function. 2) Obtain DNA samples from these 1,000 individuals and
use modern high-throughput molecular genotyping methods to create a 10 cM genetic marker
map. 3) Quantify and characterize the nature of genetic influences on CVD risk factors using
quantitative genetic methods suited for cross-sectional and serial (follow-up) data from
relatives in large extended families. 4) Conduct linkage analyses to identify chromosomal
regions (QTLs) harboring genes that influence individual variation in cardiovascular disease
risk factors. Following these linkage analyses, the investigators will examine more closely
the strongest linkage signals with fine mapping linkage analysis in order to narrow
chromosomal regions of interest. The study is a collaboration between Wright State
University and the Southwest Foundation for Biomedical Research.
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