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Researchers pool data to search for genetic risks in heart disease

Date:
October 5, 2010
Source:
American Heart Association
Summary:
Scientists analyzing pooled data from all published whole-genome studies of heart attack and coronary artery disease (CAD) has found multiple genetic mutations, including one that increases heart attack risk by 29 percent. The collective gene data could provide 10 times more subjects and controls than the largest CAD study to date.

In an unprecedented international project, researchers have found multiple genetic mutations that play a role in heart attack or coronary artery disease (CAD) risk.

The Coronary ARtery DIsease Genome-wide Replication And Meta-Analysis (CARDIoGRAM) -- published in Circulation: Cardiovascular Genetics, an American Heart Association journal -- consists of data from every published whole-genome study on genetic mutations in heart attack or CAD risk. Researchers are also pooling data from several unpublished genome-wide association studies to see if any new mutations can be uncovered.

The consortium will analyze the complete genetic profiles of more than 22,000 people of European descent with CAD or a heart attack history, and 60,000 healthy people -- 10 times more than in the next largest whole-genome study to date.

Investigators have examined an average 2.2 million single nucleotide polymorphisms (SNPs) in each of the whole-genome studies included in the review. SNPs, or "snips," are genetic variants at specific locations on individual chromosomes. Sometimes these variants manifest themselves as a disease or susceptibility to a disease. Modern technology allows hundreds of thousands of SNPs to be scanned in a person.

"Only a small proportion of the inheritability of CAD has been explained," said Heribert Schunkert, M.D., a professor of medicine at the University of Lübeck in Germany and a spokesman for CARDIoGRAM. "We have to accept that almost all persons of European ancestry carry multiple small genetic defects that mediate some coronary artery disease risk. The main aim of the consortium is to identify new disease mechanisms to improve risk prevention."

The task is challenging because of the complex nature of atherosclerosis, with multiple genetic factors contributing in small ways to the disease, he said.

Genome-wide association studies provide an unprecedented sensitivity to detect genetic variants affecting disease risk, and researchers rely on the studies' sample size. However, in a typical genome-wide association study with about 1,000 patients and controls, the power to detect a SNP with a significant effect is low.

"Collectively, our consortium increases the power of these findings 10-fold," Schunkert said. "By pooling all of the published and unpublished data, we hope to make discoveries that might have been overlooked. Given that up to 2.5 million comparisons are carried out, in parallel, for each whole-genome scan, distinguishing between true and false associations has been difficult."

The data will be maintained in a central database, and each SNP that appears related to heart disease will be subjected to replication studies to confirm its significance. Numerous SNPs and the proteins they express increase risk of CAD or heart attack. But it's unknown whether they're acting alone or with other genetic variables, Schunkert said.

"We hope that by combining all of the known whole-genome data, we will be able to provide some answers," he said.


Story Source:

The above story is based on materials provided by American Heart Association. Note: Materials may be edited for content and length.


Journal Reference:

  1. Michael Preuss, Inke R. König, John R. Thompson, Jeanette Erdmann, Devin Absher, Themistocles L. Assimes, Stefan Blankenberg, Eric Boerwinkle, Li Chen, L. Adrienne Cupples, Alistair S. Hall, Eran Halperin, Christian Hengstenberg, Hilma Holm, Reijo Laaksonen, Mingyao Li, Winfried März, Ruth McPherson, Kiran Musunuru, Christopher P. Nelson, Mary Susan Burnett, Stephen E. Epstein, Christopher J. O'Donnell, Thomas Quertermous, Daniel J. Rader, Robert Roberts, Arne Schillert, Kari Stefansson, Alexandre F.R. Stewart, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Benjamin F. Voight, George A. Wells, Andreas Ziegler, Sekar Kathiresan, Muredach P. Reilly, Nilesh J. Samani, and Heribert Schunkert. Design of the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) Study — A Genome-Wide Association Meta-Analysis Involving More than 22,000 Cases and 60,000 Controls. Circ Cardiovasc Genet, October 5, 2010 DOI: 10.1161/CIRCGENETICS.109.899443

Cite This Page:

American Heart Association. "Researchers pool data to search for genetic risks in heart disease." ScienceDaily. ScienceDaily, 5 October 2010. <www.sciencedaily.com/releases/2010/10/101005161206.htm>.
American Heart Association. (2010, October 5). Researchers pool data to search for genetic risks in heart disease. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2010/10/101005161206.htm
American Heart Association. "Researchers pool data to search for genetic risks in heart disease." ScienceDaily. www.sciencedaily.com/releases/2010/10/101005161206.htm (accessed July 31, 2014).

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