Human pedigree-based quantitative-trait-locus mapping: Localization of two genes influencing HDL-cholesterol metabolism

Laura Almasy, James E. Hixson, David L. Rainwater, Shelley Cole, Jeff T. Williams, Michael C. Mahaney, John L. VandeBerg, Michael P. Stern, Jean W. MacCluer, John Blangero

    Research output: Contribution to journalArticle

    90 Scopus citations

    Abstract

    Common disorders with genetic susceptibilities involve the action of multiple genes interacting with each other and with environmental factors, making it difficult to localize the specific genetic loci responsible. An important route to the disentangling of this complex inheritance is through the study of normal physiological variation in quantitative risk factors that may underlie liability to disease. We present an analysis of HDL-cholesterol (HDL-C), which is inversely correlated with risk of heart disease. A variety of HDL subphenotypes were analyzed, including HDL particle-size classes and the concentrations and proportions of esterified and unesterified HDL-C. Results of a complete genomic screen in large, randomly ascertained pedigrees implicated two loci, one on chromosome 8 and the other on chromosome 15, that influence a component of HDL-C - namely, unesterified HDL(2a)-C. Multivariate analyses of multiple HDL phenotypes and simultaneous multilocus analysis of the quantitative-trait loci identified permit further characterization of the genetic effects on HDL-C. These analyses suggest that the action of the chromosome 8 locus is specific to unesterified cholesterol levels, whereas the chromosome 15 locus appears to influence both HDL-C concentration and distribution of cholesterol among HDL particle sizes.

    Original languageEnglish (US)
    Pages (from-to)1686-1693
    Number of pages8
    JournalAmerican Journal of Human Genetics
    Volume64
    Issue number6
    DOIs
    StatePublished - Jan 1 1999

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

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    Almasy, L., Hixson, J. E., Rainwater, D. L., Cole, S., Williams, J. T., Mahaney, M. C., VandeBerg, J. L., Stern, M. P., MacCluer, J. W., & Blangero, J. (1999). Human pedigree-based quantitative-trait-locus mapping: Localization of two genes influencing HDL-cholesterol metabolism. American Journal of Human Genetics, 64(6), 1686-1693. https://doi.org/10.1086/302425