Design of the Genetics of Early Onset Cardiovascular Disease (GENECARD) study

Background Coronary artery disease (CAD) is the leading cause of death and a leading cause of disability in the developed world. Early onset (premature) coronary artery disease (EOCAD) is known to have a particularly strong genetic component. However, the actual genes leading to this increased risk...

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Bibliographic Details
Published in:	The American heart journal 2003-04, Vol.145 (4), p.602-613
Main Authors:	Hauser, Elizabeth R., Mooser, Vincent, Crossman, David C., Haines, Jonathan L., Jones, Christopher H., Winkelmann, Bernhard R., Schmidt, Silke, Scott, William K., Roses, Allen D., Pericak-Vance, Margaret A., Granger, Christopher B., Kraus, William E.
Format:	Article
Language:	eng
Subjects:	Adult Age of Onset Biological and medical sciences Cardiology. Vascular system Coronary Disease - diagnosis Coronary Disease - genetics Coronary heart disease Environment Family Characteristics Female Genetic Linkage Genetic Predisposition to Disease Heart Humans Male Medical sciences Middle Aged Risk Factors Siblings
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Summary:	Background Coronary artery disease (CAD) is the leading cause of death and a leading cause of disability in the developed world. Early onset (premature) coronary artery disease (EOCAD) is known to have a particularly strong genetic component. However, the actual genes leading to this increased risk of CAD remain obscure. Methods The primary goal of the Genetics of Early Onset Cardiovascular Disease (GENECARD) study is to perform a genetic linkage study in 920 families with at least 1 sibling pair having EOCAD. The study sites include a US network of 15 cardiology practices and 5 additional sites located in Europe and the United States. We propose to identify chromosomal regions associated with increased susceptibility to EOCAD in this large sample of affected sibling pairs and nuclear families, where EOCAD is defined on the basis of having acute coronary syndrome (unstable angina or myocardial infarction), a revascularization procedure, or a positive functional imaging study at or before the age of 50 years in men or 55 years in women. To identify which genomic regions and genes are associated with increased susceptibility to EOCAD, we will use a comprehensive strategy comprising genomic screening, fine mapping, candidate gene analysis, and family-based association studies. Results Herein we describe the clinical characteristics, family history, and risk factor profiles of the 1168 members from 438 nuclear families included in the first, exploratory analysis. Analysis of the study population revealed a strong concordance of known cardiac risk factors among affected sibling pairs. There was significant concordance ( P
ISSN:	0002-8703 1097-6744