title: A comprehensive linkage analysis for myocardial infarction and its related risk factors.
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.
authors.affiliation: Department of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Broeckel
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
authors.forename: Björn
authors.initials: B
authors.lastname: Mayer
authors.forename: Stephan
authors.initials: S
authors.lastname: Holmer
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Martin
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: André
authors.initials: A
authors.lastname: Reis
authors.forename: Günter A J
authors.initials: GA
authors.lastname: Riegger
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Jacob
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
mesh_terms: D000368:Aged; D001054:Apolipoproteins A / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D006973:Hypertension / Q000235:genetics; D017270:Lipoprotein(a) / Q000097:blood; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000235:genetics*; D010641:Phenotype; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D001054:Apolipoproteins A; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017270:Lipoprotein(a); D014280:Triglycerides