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

Details

Serval ID
serval:BIB_BFE17EB9D512
Type
Article: article from journal or magazin.
Collection
Publications
Title
Serum lipids in the GENECARD study of coronary artery disease identify quantitative trait loci and phenotypic subsets on chromosomes 3q and 5q.
Journal
Annals of Human Genetics
Author(s)
Shah S.H., Kraus W.E., Crossman D.C., Granger C.B., Haines J.L., Jones C.J., Mooser V., Huang L., Haynes C., Dowdy E., Vega G.L., Grundy S.M., Vance J.M., Hauser E.R.
ISSN
0003-4800 (Print)
ISSN-L
0003-4800
Publication state
Published
Issued date
2006
Volume
70
Number
Pt 6
Pages
738-748
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support
Abstract
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.
Keywords
Adult, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 5, Coronary Artery Disease/diagnosis, Coronary Artery Disease/genetics, Female, Genetic Linkage, Genetic Variation, Humans, Lipoproteins/blood, Lipoproteins/genetics, Lod Score, Male, Middle Aged, Phenotype, Quantitative Trait Loci
Pubmed
Web of science
Create date
13/10/2013 22:08
Last modification date
20/08/2019 16:34
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