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International Team Launches Heart Disease GWAS Meta-Analysis

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – An international research team is undertaking a meta-analysis that will integrate data from all of the published genome-wide studies of heart attack and other forms of coronary artery disease in individuals of European ancestry.

The study, dubbed the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis, or CaRDIoGRAM, will include published and unpublished data on more than 22,000 heart disease cases and 60,000 healthy controls. The researchers presented their approach — along with proof-of-principle findings for one newly identified heart attack risk SNP — in the online version of the journal Circulation: Cardiovascular Genetics yesterday.

"[A]lmost all persons of European ancestry carry multiple small genetic defects that mediate some coronary artery disease risk," study spokesman Heribert Schunkert, a medical researcher at Germany's University of Lubeck, said in a statement. "The main aim of the consortium is to identify new disease mechanisms to improve risk prevention."

By combining data generated through the Wellcome Trust Case Control Consortium, the Atherosclerotic Disease Vascular Function and Genetic Epidemiology study, and several other prominent studies, the team hopes to dramatically improve their ability to find otherwise undetectable variants that dial up heart disease risk.

"Collectively, our consortium provides more than ten times the number of cases and controls than the largest published individual [coronary artery disease] GWAS," the team wrote. "Consequently, our meta-analysis will have increased power to detect small genetic effects."

The study will assess data on individuals of European ancestry enrolled through case-control or prospective studies of heart disease. Researchers will have access to individuals' heart attack and/or coronary artery disease phenotype data as well as genotype information — generated using either Affymetrix or Illumina arrays combined with imputation — for an average of 2.2 million SNPs per study.

To highlight the feasibility of their approach, the researchers presented data on one new heart attack risk SNP on chromosome 9 already detected using such an approach. The variant, which falls in a region containing three coronary artery disease SNPs, was not identified in past GWAS but does show up through meta-analysis.

The researchers' findings suggest the heart attack associated SNP rs1333049, found in the chromosome 9 locus 9p21, can ramp up the risk of myocardial infarction by an estimated 29 percent. And they noted, results so far suggest the variant has stronger effects in younger individuals than in older individuals.

For their larger analyses, the team plans to validate possible risk SNPs and also categorize them based on their level of association — information that is expected to help guide follow-up studies of the variants.

In addition, those involved in the study are looking at possible genetic heterogeneity related to heart disease by doing analyses of various participant sub-groups, including groups defined by age of disease onset, sex, and so on.

Data from the CaRDIoGRAM study will reportedly be made available to other researchers through the Cardiogenics Consortium database.

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