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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 and Watkins, Hugh (2006) Genome-Wide Mapping of Susceptibility to Coronary Artery Disease Identifies a Novel Replicated Locus on Chromosome 17 PLoS Genetics, 2 (5 e72). 0755-0761.

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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; p¼0.009 after adjustment for three independent replication tests). An exclusion analysis suggests that further genes of effect size ksib . 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.

Item Type: Article
Additional Information: © 2006 Farrall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Divisions: Faculty of Health and Medical Sciences > Biochemistry and Physiology
Depositing User: Melanie Hughes
Date Deposited: 26 Oct 2010 13:41
Last Modified: 23 Sep 2013 18:39
URI: http://epubs.surrey.ac.uk/id/eprint/2564

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