Faculty Collaboration Database

A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nat Genet 2002 Feb;30(2):210-4

Date

01/31/2002

Pubmed ID

11818963

DOI

10.1038/ng827

Scopus ID

2-s2.0-18544372620 (requires institutional sign-in at Scopus site)   287 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.

Author List

Broeckel U, Hengstenberg C, Mayer B, Holmer S, Martin LJ, Comuzzie AG, Blangero J, Nürnberg P, Reis A, Riegger GA, Jacob HJ, Schunkert H

Author

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Apolipoproteins A
Cholesterol, HDL
Cholesterol, LDL
Chromosome Mapping
Chromosomes, Human, Pair 14
Coronary Artery Disease
Diabetes Mellitus
Female
Genetic Linkage
Humans
Hypertension
Lipoprotein(a)
Lod Score
Male
Middle Aged
Myocardial Infarction
Phenotype
Risk Factors
Triglycerides