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Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):1942-50. Epub 2004 Aug 26.

Low-density lipoprotein particle size loci in familial combined hyperlipidemia: evidence for multiple loci from a genome scan.

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  • 1Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, USA.

Abstract

OBJECTIVE:

Low-density lipoprotein (LDL) size is associated with vascular disease and with familial combined hyperlipidemia (FCHL).

METHODS AND RESULTS:

We used logarithm of odds (lod) score and Bayesian Markov chain Monte Carlo (MCMC) linkage analysis methods to perform a 10-cM genome scan of LDL size, measured as peak particle diameter (PPD) and adjusted for age, sex, body mass index, and triglycerides in 4 large families with FCHL (n=185). We identified significant evidence of linkage to a chromosome 9p locus (multipoint lod(max)=3.70; MCMC intensity ratio [IR]=21) in a single family, and across all 4 families to chromosomes 16q23 (lod(max)=3.00; IR=43) near cholesteryl ester transfer protein (CETP) and to 11q22 (lod(max)=3.71; IR=120). Chromosome 14q24-31, a region with previous suggestive LDL PPD linkage evidence, yielded an IR of 71 but an lod(max)=1.79 in the combined families.

CONCLUSIONS:

These results of significant evidence of linkage to 3 regions (9p, 16q, and 11q) and confirmatory support of previous reported linkage to 14q in large FCHL pedigrees demonstrate that LDL size is a trait influenced by multiple loci and illustrate the complementary use of lod score and MCMC methods in analysis of a complex trait.

PMID:
15331429
[PubMed - indexed for MEDLINE]
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