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Abstract: 500 THE GENETICS OF ATHEROSCLEROSIS
Plenary Session II - Pathogenesis of Atherosclerosis and Risk Factors Abstract: 500 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
THE GENETICS OF ATHEROSCLEROSIS R McPherson, O Jarinova, L Chen, A Stewart Cardiology, University of Ottawa Heart Institute, Ottawa, On In the last two years, considerable progress has been made in understanding the genetic basis of coronary artery disease CAD and its metabolic precedents using both candidate gene and genome wide association studies (GWAS). GWAS provide an unbiased approach that has led to the identifiation of novel loci associated with several complex phenotypes including CAD. Notably, many of these were unanticipated based on prior knowledge. We and others identified an intergenic 58 kb locus on 9p21, that is robustly associated with CAD risk. 25% of Europeans are homozygous carriers of the risk allele and have a 2 fold increased risk for premature CAD, that is independent of all known CAD risk factors, implying a novel biological pathway relevant to atherosclerosis. Other CAD loci replicated in the Ottawa Heart Study and other cohorts include: 1q41 (MIA3), 8p21 (LPL), 19q13 (APOC1). However, despite the recent successes of the GWAS approach, the ability to identify the genetic basis of complex disease remains modest. Current GWAS technology is limited by reliance on HapMap, based on genetic data from a small number of individuals and designed to detect only common alleles despite the observation that numerous rare alleles contribute significantly to predisposition for disease. In addition, GWAS cannot identify the causative sequence variation responsible for disease predisposition and provide limited insight into the function of genetic variants. Thus considerable effort will be required over the next decade to both identify causative genetic variants by deep resequencing and determine functional effects at the cellular and whole animal levels. Funding: Canadian Institutes of Health Research, Heart & Stroke Foundation of Ontario
THE GENETICS OF ATHEROSCLEROSIS R McPherson, O Jarinova, L Chen, A Stewart Cardiology, University of Ottawa Heart Institute, Ottawa, On In the last two years, considerable progress has been made in understanding the genetic basis of coronary artery disease CAD and its metabolic precedents using both candidate gene and genome wide association studies (GWAS). GWAS provide an unbiased approach that has led to the identifiation of novel loci associated with several complex phenotypes including CAD. Notably, many of these were unanticipated based on prior knowledge. We and others identified an intergenic 58 kb locus on 9p21, that is robustly associated with CAD risk. 25% of Europeans are homozygous carriers of the risk allele and have a 2 fold increased risk for premature CAD, that is independent of all known CAD risk factors, implying a novel biological pathway relevant to atherosclerosis. Other CAD loci replicated in the Ottawa Heart Study and other cohorts include: 1q41 (MIA3), 8p21 (LPL), 19q13 (APOC1). However, despite the recent successes of the GWAS approach, the ability to identify the genetic basis of complex disease remains modest. Current GWAS technology is limited by reliance on HapMap, based on genetic data from a small number of individuals and designed to detect only common alleles despite the observation that numerous rare alleles contribute significantly to predisposition for disease. In addition, GWAS cannot identify the causative sequence variation responsible for disease predisposition and provide limited insight into the function of genetic variants. Thus considerable effort will be required over the next decade to both identify causative genetic variants by deep resequencing and determine functional effects at the cellular and whole animal levels. Funding: Canadian Institutes of Health Research, Heart & Stroke Foundation of Ontario