A comprehensive linkage analysis for myocardial infarction and its related risk factors

Ulrich Broeckel, Christian Hengstenberg, Björn Mayer, Stephan Holmer, Lisa J. Martin, Anthony G. Comuzzie, John Blangero, Peter Nürnberg, André Reis, Günter A.J. Riegger, Howard J. Jacob, Heribert Schunkert

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    273 Scopus citations

    Abstract

    Coronary artery disease and myocardial infarction (MI) are leading causes of death in the western world. Numerous studies have shown that risk factors such as diabetes mellitus, arterial hypertension and hypercholesterolemia contribute to the development of the disease. Although each risk factor by itself is partly under genetic control, a positive family history is an independent predictor, which suggests that there are additional susceptibility genes. We have scanned the whole genome in 513 families to identify chromosomal regions linked to myocardial infarction and related risk factors that are known to be under genetic control. Here we show, by using variance component analysis and incorporating risk factors, that risk of myocardial infarction maps to a single region on chromosome 14 with a significant lod score of 3.9 (pointwise P=0.00015, genome-wide P<0.05), providing evidence of a principal MI locus. To characterize this locus we analyzed each risk factor by itself. Serum concentrations of lipoprotein (a) show linkage to both the apolipoprotein (a) locus (lod score 26.99) and a new locus on chromosome 1 (lod score 3.8). There is suggestive linkage for diabetes mellitus on chromosome 6 (lod score 2.96), for hypertension on chromosomes 1 and 6, for high-density and low-density lipoprotein cholesterol on chromosomes 1 and 17, and for triglyceride concentrations on chromosome 9. Although some of these risk factors overlap with previously identified loci, none overlaps with the newly identified susceptibility locus for myocardial infarction and coronary artery disease.

    Original languageEnglish (US)
    Pages (from-to)210-214
    Number of pages5
    JournalNature Genetics
    Volume30
    Issue number2
    DOIs
    StatePublished - Feb 2002

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    ASJC Scopus subject areas

    • Genetics

    Cite this

    Broeckel, U., Hengstenberg, C., Mayer, B., Holmer, S., Martin, L. J., Comuzzie, A. G., Blangero, J., Nürnberg, P., Reis, A., Riegger, G. A. J., Jacob, H. J., & Schunkert, H. (2002). A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nature Genetics, 30(2), 210-214. https://doi.org/10.1038/ng827