Genome-wide mapping of susceptibility to coronary artery disease identifies a novel replicated locus on chromosome 17.

Martin Farrall, Fiona R. Green, John F. Peden, Per G. Olsson, Robert Clarke, Mai Lis Hellenius, Stephan Rust, Jacob Lagercrantz, Maria Grazia Franzosi, Helmut Schulte, Alisoun Carey, Gunnar Olsson, Gerd Assmann, Gianni Tognoni, Rory Collins, Anders Hamsten, Hugh Watkins

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Coronary artery disease (CAD) is a leading cause of death world-wide, and most cases have a complex, multifactorial aetiology that includes a substantial heritable component. Identification of new genes involved in CAD may inform pathogenesis and provide new therapeutic targets. The PROCARDIS study recruited 2,658 affected sibling pairs (ASPs) with onset of CAD before age 66 y from four European countries to map susceptibility loci for CAD. ASPs were defined as having CAD phenotype if both had CAD, or myocardial infarction (MI) phenotype if both had a MI. In a first study, involving a genome-wide linkage screen, tentative loci were mapped to Chromosomes 3 and 11 with the CAD phenotype (1,464 ASPs), and to Chromosome 17 with the MI phenotype (739 ASPs). In a second study, these loci were examined with a dense panel of grid-tightening markers in an independent set of families (1,194 CAD and 344 MI ASPs). This replication study showed a significant result on Chromosome 17 (MI phenotype; p = 0.009 after adjustment for three independent replication tests). An exclusion analysis suggests that further genes of effect size lambda(sib) > 1.24 are unlikely to exist in these populations of European ancestry. To our knowledge, this is the first genome-wide linkage analysis to map, and replicate, a CAD locus. The region on Chromosome 17 provides a compelling target within which to identify novel genes underlying CAD. Understanding the genetic aetiology of CAD may lead to novel preventative and/or therapeutic strategies.

Original languageEnglish
JournalPLoS Genetics
Volume2
Issue number5
DOIs
Publication statusPublished - May 2006

Fingerprint

Chromosomes, Human, Pair 17
Chromosome Mapping
Coronary Artery Disease
chromosome
genome
chromosomes
loci
myocardial infarction
phenotype
Myocardial Infarction
Phenotype
etiology
linkage (genetics)
gene
coronary artery disease
Genome
Genes
therapeutics
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 3

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Farrall, M., Green, F. R., Peden, J. F., Olsson, P. G., Clarke, R., Hellenius, M. L., ... Watkins, H. (2006). Genome-wide mapping of susceptibility to coronary artery disease identifies a novel replicated locus on chromosome 17. PLoS Genetics, 2(5). https://doi.org/10.1371/journal.pgen.0020072

Genome-wide mapping of susceptibility to coronary artery disease identifies a novel replicated locus on chromosome 17. / Farrall, Martin; Green, Fiona R.; Peden, John F.; Olsson, Per G.; Clarke, Robert; Hellenius, Mai Lis; Rust, Stephan; Lagercrantz, Jacob; Franzosi, Maria Grazia; Schulte, Helmut; Carey, Alisoun; Olsson, Gunnar; Assmann, Gerd; Tognoni, Gianni; Collins, Rory; Hamsten, Anders; Watkins, Hugh.

In: PLoS Genetics, Vol. 2, No. 5, 05.2006.

Research output: Contribution to journalArticle

Farrall, M, Green, FR, Peden, JF, Olsson, PG, Clarke, R, Hellenius, ML, Rust, S, Lagercrantz, J, Franzosi, MG, Schulte, H, Carey, A, Olsson, G, Assmann, G, Tognoni, G, Collins, R, Hamsten, A & Watkins, H 2006, 'Genome-wide mapping of susceptibility to coronary artery disease identifies a novel replicated locus on chromosome 17.', PLoS Genetics, vol. 2, no. 5. https://doi.org/10.1371/journal.pgen.0020072
Farrall, Martin ; Green, Fiona R. ; Peden, John F. ; Olsson, Per G. ; Clarke, Robert ; Hellenius, Mai Lis ; Rust, Stephan ; Lagercrantz, Jacob ; Franzosi, Maria Grazia ; Schulte, Helmut ; Carey, Alisoun ; Olsson, Gunnar ; Assmann, Gerd ; Tognoni, Gianni ; Collins, Rory ; Hamsten, Anders ; Watkins, Hugh. / Genome-wide mapping of susceptibility to coronary artery disease identifies a novel replicated locus on chromosome 17. In: PLoS Genetics. 2006 ; Vol. 2, No. 5.
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