A genomewide scan for early-onset coronary artery disease in 438 families: the GENECARD Study

Elizabeth R. Hauser, David C. Crossman, Christopher B. Granger, Jonathan L. Haines, Christopher J. H. Jones, Vincent Mooser, Brendan McAdam, Bernhard R. Winkelmann, Alan H. Wiseman, J. Brent Muhlestein, Alan G. Bartel, Charles A. Dennis, Elaine Dowdy, Susan Estabrooks, Karen Eggleston, Sheila Francis, Kath Roche, Paula W. Clevenger, Liling Huang, Bonnie PedersenSvati Shah, Silke Schmidt, Carol Haynes, Sandra West, Donny Asper, Michael Booze, Sanjay Sharma, Scott Sundseth, Lefkos Middleton, Allen D. Roses, Michael A. Hauser, Jeffery M. Vance, Margaret A. Pericak-Vance, William E. Kraus

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A family history of coronary artery disease (CAD), especially when the disease occurs at a young age, is a potent risk factor for CAD. DNA collection in families in which two or more siblings are affected at an early age allows identification of genetic factors for CAD by linkage analysis. We performed a genomewide scan in 1,168 individuals from 438 families, including 493 affected sibling pairs with documented onset of CAD before 51 years of age in men and before 56 years of age in women. We prospectively defined three phenotypic subsets of families: (1) acute coronary syndrome in two or more siblings; (2) absence of type 2 diabetes in all affected siblings; and (3) atherogenic dyslipidemia in any one sibling. Genotypes were analyzed for 395 microsatellite markers. Regions were defined as providing evidence for linkage if they provided parametric two-point LOD scores >1.5, together with nonparametric multipoint LOD scores >1.0. Regions on chromosomes 3q13 (multipoint LOD = 3.3; empirical P value
Original languageEnglish
Pages (from-to)436-447
Number of pages12
JournalAmerican Journal of Human Genetics
Issue number3
Publication statusPublished - Sep 2004

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