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

Research output: Contribution to journalArticle

272 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Lod Score
Myocardial Infarction
Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 6
Coronary Artery Disease
Diabetes Mellitus
Genome
Hypertension
Apoprotein(a)
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 9
Western World
Chromosomes, Human, Pair 17
Lipoprotein(a)
Hypercholesterolemia
LDL Cholesterol
Cause of Death
Analysis of Variance
Triglycerides
Serum

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Broeckel, U., Hengstenberg, C., Mayer, B., Holmer, S., Martin, L. J., Comuzzie, A. G., ... 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

A comprehensive linkage analysis for myocardial infarction and its related risk factors. / Broeckel, Ulrich; Hengstenberg, Christian; Mayer, Björn; Holmer, Stephan; Martin, Lisa J.; Comuzzie, Anthony G.; Blangero, John; Nürnberg, Peter; Reis, André; Riegger, Günter A J; Jacob, Howard J.; Schunkert, Heribert.

In: Nature Genetics, Vol. 30, No. 2, 02.2002, p. 210-214.

Research output: Contribution to journalArticle

Broeckel, U, Hengstenberg, C, Mayer, B, Holmer, S, Martin, LJ, Comuzzie, AG, Blangero, J, Nürnberg, P, Reis, A, Riegger, GAJ, Jacob, HJ & Schunkert, H 2002, 'A comprehensive linkage analysis for myocardial infarction and its related risk factors', Nature Genetics, vol. 30, no. 2, pp. 210-214. https://doi.org/10.1038/ng827
Broeckel U, Hengstenberg C, Mayer B, Holmer S, Martin LJ, Comuzzie AG et al. A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nature Genetics. 2002 Feb;30(2):210-214. https://doi.org/10.1038/ng827
Broeckel, Ulrich ; Hengstenberg, Christian ; Mayer, Björn ; Holmer, Stephan ; Martin, Lisa J. ; Comuzzie, Anthony G. ; Blangero, John ; Nürnberg, Peter ; Reis, André ; Riegger, Günter A J ; Jacob, Howard J. ; Schunkert, Heribert. / A comprehensive linkage analysis for myocardial infarction and its related risk factors. In: Nature Genetics. 2002 ; Vol. 30, No. 2. pp. 210-214.
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