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Serum lipids in the GENECARD study of coronary artery disease identify quantitative trait loci and phenotypic subsets on chromosomes 3q and 5q.

Publication ,  Journal Article
Shah, SH; Kraus, WE; Crossman, DC; Granger, CB; Haines, JL; Jones, CJH; Mooser, V; Huang, L; Haynes, C; Dowdy, E; Vega, GL; Grundy, SM ...
Published in: Ann Hum Genet
November 2006

Coronary artery disease (CAD) and dyslipidemia have strong genetic components. Heterogeneity complicates evaluating genetics of complex diseases such as CAD; incorporating disease-related phenotypes may help reduce heterogeneity. We hypothesized that incorporating lipoproteins in a study of CAD would increase the power to map genes, narrow linkage peaks, identify phenotypic subsets, and elucidate the contribution of established risk factors to genetic results. We performed ordered subset analysis (OSA) and quantitative trait linkage (QTL) using serum lipoproteins and microsatellite markers in 346 families with early-onset CAD. OSA defined homogeneous subsets and calculated lod scores across a chromosome after ranking families by mean lipoprotein values. QTL used variance components analysis. We found significantly increased linkage to chromosome 3q13 (LOD 5.10, p = 0.008) in families with higher HDL cholesterol, lower LDL and total cholesterol, lower triglycerides, and fewer CAD risk factors, possibly due to a concentrated non-lipoprotein-related genetic effect. OSA identified linkage on chromosome 5q34 in families with higher cholesterol, possibly representing a hereditary lipoprotein phenotype. Multiple QTLs were identified, with the strongest for: total cholesterol on chromosome 5q14 (LOD 4.3); LDL on 20p12 (LOD 3.97); HDL on 3p14 (LOD 1.65); triglycerides on 18q22 (LOD 1.43); and HDL/TC ratio on 3q27-28 (LOD 2.06). Our findings suggest the presence of etiologic heterogeneity in families with early-onset CAD, potentially due to differential effects of lipoprotein phenotypes. Candidate genes are under investigation.

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Published In

Ann Hum Genet

DOI

ISSN

0003-4800

Publication Date

November 2006

Volume

70

Issue

Pt 6

Start / End Page

738 / 748

Location

England

Related Subject Headings

  • Quantitative Trait Loci
  • Phenotype
  • Middle Aged
  • Male
  • Lod Score
  • Lipoproteins
  • Humans
  • Genetics & Heredity
  • Genetic Variation
  • Genetic Linkage
 

Citation

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Shah, S. H., Kraus, W. E., Crossman, D. C., Granger, C. B., Haines, J. L., Jones, C. J. H., … Hauser, E. R. (2006). Serum lipids in the GENECARD study of coronary artery disease identify quantitative trait loci and phenotypic subsets on chromosomes 3q and 5q. Ann Hum Genet, 70(Pt 6), 738–748. https://doi.org/10.1111/j.1469-1809.2006.00288.x
Shah, S. H., W. E. Kraus, D. C. Crossman, C. B. Granger, J. L. Haines, C. J. H. Jones, V. Mooser, et al. “Serum lipids in the GENECARD study of coronary artery disease identify quantitative trait loci and phenotypic subsets on chromosomes 3q and 5q.Ann Hum Genet 70, no. Pt 6 (November 2006): 738–48. https://doi.org/10.1111/j.1469-1809.2006.00288.x.
Shah SH, Kraus WE, Crossman DC, Granger CB, Haines JL, Jones CJH, et al. Serum lipids in the GENECARD study of coronary artery disease identify quantitative trait loci and phenotypic subsets on chromosomes 3q and 5q. Ann Hum Genet. 2006 Nov;70(Pt 6):738–48.
Shah, S. H., et al. “Serum lipids in the GENECARD study of coronary artery disease identify quantitative trait loci and phenotypic subsets on chromosomes 3q and 5q.Ann Hum Genet, vol. 70, no. Pt 6, Nov. 2006, pp. 738–48. Pubmed, doi:10.1111/j.1469-1809.2006.00288.x.
Shah SH, Kraus WE, Crossman DC, Granger CB, Haines JL, Jones CJH, Mooser V, Huang L, Haynes C, Dowdy E, Vega GL, Grundy SM, Vance JM, Hauser ER. Serum lipids in the GENECARD study of coronary artery disease identify quantitative trait loci and phenotypic subsets on chromosomes 3q and 5q. Ann Hum Genet. 2006 Nov;70(Pt 6):738–748.
Journal cover image

Published In

Ann Hum Genet

DOI

ISSN

0003-4800

Publication Date

November 2006

Volume

70

Issue

Pt 6

Start / End Page

738 / 748

Location

England

Related Subject Headings

  • Quantitative Trait Loci
  • Phenotype
  • Middle Aged
  • Male
  • Lod Score
  • Lipoproteins
  • Humans
  • Genetics & Heredity
  • Genetic Variation
  • Genetic Linkage