on August 26, 2004
Published online before print August 26, 2004, doi: 10.1161/01.ATV.0000143499.09575.93
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Submitted on July 30, 2004
Accepted on August 10, 2004
Low-Density Lipoprotein Particle Size Loci in Familial Combined Hyperlipidemia. Evidence for Multiple Loci From a Genome Scan
Michael D. Badzioch ;
From the Department of Medicine, Divisions of Medical Genetics (M.D.B., R.P.I., F.G., A.G.M., E.M.W., G.P.J.) and Metabolism, Endocrinology, and Nutrition (J.D.B.), Departments of Genome Science (A.G.M., E.M.W., G.P.J.) and Biostatistics (R.P.I., E.M.W.), University of Washington, Seattle; Department of Epidemiology and Community Medicine (F.G.), University of Ottawa, Ontario, Canada; and Life Sciences Division (R.M.K.), Ernest Orlando Lawrence Berkeley National Laboratory, University of California, Berkeley.
* To whom correspondence should be addressed. E-mail: pair{at}u.washington.edu.
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 lodmax=3.70; MCMC intensity ratio [IR]=21) in a single family, and across all 4 families to chromosomes 16q23 (lodmax=3.00; IR=43) near cholesteryl ester transfer protein (CETP) and to 11q22 (lodmax=3.71; IR=120). Chromosome 14q24-31, a region with previous suggestive LDL PPD linkage evidence, yielded an IR of 71 but an lodmax=1.79 in the combined families.
Conclusions--These results of significant evidence of linkage to 3 regions (9p, 16q, and 11q) and support confirmation 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.
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