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

Publication ,  Journal Article
Hauser, ER; Crossman, DC; Granger, CB; Haines, JL; Jones, CJH; Mooser, V; McAdam, B; Winkelmann, BR; Wiseman, AH; Muhlestein, JB; Bartel, AG ...
Published in: Am J Hum Genet
September 2004

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.

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Published In

Am J Hum Genet

DOI

ISSN

0002-9297

Publication Date

September 2004

Volume

75

Issue

3

Start / End Page

436 / 447

Location

United States

Related Subject Headings

  • Phenotype
  • Models, Genetic
  • Middle Aged
  • Microsatellite Repeats
  • Male
  • Lod Score
  • Humans
  • Genotype
  • Genome, Human
  • Genome
 

Citation

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Hauser, E. R., Crossman, D. C., Granger, C. B., Haines, J. L., Jones, C. J. H., Mooser, V., … Kraus, W. E. (2004). A genomewide scan for early-onset coronary artery disease in 438 families: the GENECARD Study. Am J Hum Genet, 75(3), 436–447. https://doi.org/10.1086/423900
Hauser, Elizabeth R., David C. Crossman, Christopher B. Granger, Jonathan L. Haines, Christopher J. H. Jones, Vincent Mooser, Brendan McAdam, et al. “A genomewide scan for early-onset coronary artery disease in 438 families: the GENECARD Study.Am J Hum Genet 75, no. 3 (September 2004): 436–47. https://doi.org/10.1086/423900.
Hauser ER, Crossman DC, Granger CB, Haines JL, Jones CJH, Mooser V, et al. A genomewide scan for early-onset coronary artery disease in 438 families: the GENECARD Study. Am J Hum Genet. 2004 Sep;75(3):436–47.
Hauser, Elizabeth R., et al. “A genomewide scan for early-onset coronary artery disease in 438 families: the GENECARD Study.Am J Hum Genet, vol. 75, no. 3, Sept. 2004, pp. 436–47. Pubmed, doi:10.1086/423900.
Hauser ER, Crossman DC, Granger CB, Haines JL, Jones CJH, Mooser V, McAdam B, Winkelmann BR, Wiseman AH, Muhlestein JB, Bartel AG, Dennis CA, Dowdy E, Estabrooks S, Eggleston K, Francis S, Roche K, Clevenger PW, Huang L, Pedersen B, Shah S, Schmidt S, Haynes C, West S, Asper D, Booze M, Sharma S, Sundseth S, Middleton L, Roses AD, Hauser MA, Vance JM, Pericak-Vance MA, Kraus WE. A genomewide scan for early-onset coronary artery disease in 438 families: the GENECARD Study. Am J Hum Genet. 2004 Sep;75(3):436–447.
Journal cover image

Published In

Am J Hum Genet

DOI

ISSN

0002-9297

Publication Date

September 2004

Volume

75

Issue

3

Start / End Page

436 / 447

Location

United States

Related Subject Headings

  • Phenotype
  • Models, Genetic
  • Middle Aged
  • Microsatellite Repeats
  • Male
  • Lod Score
  • Humans
  • Genotype
  • Genome, Human
  • Genome