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

研究成果: 雜誌貢獻文章

129 引文 斯高帕斯(Scopus)

摘要

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 <.001) and 5q31 (multipoint LOD = 1.4; empirical P value <.081) met these criteria in the entire data set, and regions on chromosomes 1q25, 3q13, 7p14, and 19p13 met these criteria in one or more of the subsets. Two regions, 3q13 and 1q25, met the criteria for genomewide significance. We have identified a region on chromosome 3q13 that is linked to early-onset CAD, as well as additional regions of interest that will require further analysis. These data provide initial areas of the human genome where further investigation may reveal susceptibility genes for early-onset CAD.
原文英語
頁(從 - 到)436-447
頁數12
期刊American Journal of Human Genetics
75
發行號3
DOIs
出版狀態已發佈 - 一月 1 2004
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

引用此

Hauser, E. R., Crossman, D. C., Granger, C. B., Haines, J. L., Jones, C. J. H., Mooser, V., McAdam, B., Winkelmann, B. R., Wiseman, A. H., Muhlestein, J. B., Bartel, A. G., Dennis, C. A., Dowdy, E., Estabrooks, S., Eggleston, K., Francis, S., Roche, K., Clevenger, P. W., Huang, L., ... Kraus, W. E. (2004). A genomewide scan for early-onset coronary artery disease in 438 families: The GENECARD study. American Journal of Human Genetics, 75(3), 436-447. https://doi.org/10.1086/423900