A Major Locus Influencing Plasma High-Density Lipoprotein Cholesterol Levels in the San Antonio Family Heart Study Segregation and Linkage Analyses

Michael C. Mahaney, John Blangero, David L. Rainwater, Anthony G. Comuzzie, John L. VandeBerg, Michael P. Stern, Jean W. MacCluer, James E. Hixson

    Research output: Contribution to journalArticle

    65 Scopus citations

    Abstract

    To detect and measure the effects of a single locus on quantitative variation in plasma concentrations of HDL cholesterol (HDL-C), we conducted statistical genetic analyses on data from 526 Mexican American individuals in 25 randomly ascertained pedigrees. By using maximum-likelihood complex segregation analysis, we found evidence for a major locus with a codominant mixture model that included the phenotypic means, standard deviations, relative frequency of a low HDL-C allele, and heritability for plasma HDL-C levels, plus the effects of sex (genotype specific), age-by-sex, age2-by-sex, plasma concentrations of apolipoprotein (apo)AI and triglycerides (genotype specific), exogenous sex hormone use, and menopausal status under an unrestricted general model. Inclusion of the four covariates (in addition to the sex and age-by-sex effects) accounted for nearly 79% of the variance in total plasma HDL-C levels. Of the remaining 21% of the variance, the detected major locus accounted for approximately 55% in men and 21% in women; the total genetic contributions to the variance by genes were approximately 82% in men and 69% in women. Linkage analyses with penetrance parameter estimates from the segregation analysis excluded tight linkage between the detected major locus and markers for the following candidate loci: the apoAI/apoCIII genomic region (P<.05), apoB (P<.01), hepatic lipase (P<.001), lipoprotein lipase (P<.001), and the LDL receptor (P<.001). While not excluding the apoE locus (LOD=-0.348, P<.21), the analysis provided no support for tight linkage between it and the detected major locus.

    Original languageEnglish (US)
    Pages (from-to)1730-1739
    Number of pages10
    JournalArteriosclerosis, Thrombosis, and Vascular Biology
    Volume15
    Issue number10
    DOIs
    StatePublished - Oct 1995

    Keywords

    • Candidate genes
    • Genetic epidemiology
    • HDL cholesterol
    • Inheritance
    • Linkage

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

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    Mahaney, M. C., Blangero, J., Rainwater, D. L., Comuzzie, A. G., VandeBerg, J. L., Stern, M. P., MacCluer, J. W., & Hixson, J. E. (1995). A Major Locus Influencing Plasma High-Density Lipoprotein Cholesterol Levels in the San Antonio Family Heart Study Segregation and Linkage Analyses. Arteriosclerosis, Thrombosis, and Vascular Biology, 15(10), 1730-1739. https://doi.org/10.1161/01.ATV.15.10.1730