Researchers pool data to search for genetic risks in heart disease

Oct 05, 2010

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 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 Researchers are also pooling data from several unpublished genome-wide association studies to see if any new mutations can be uncovered.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 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 "By pooling all of the published and unpublished data, we hope to make discoveries that might have been overlooked.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 . 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.

Explore further: Changes in scores of genes contribute to autism risk

add to favorites email to friend print save as pdf

Related Stories

Are we selling personalized medicine before its time?

Feb 06, 2009

We may be a long way off from using genetics to reliably gauge our risks for specific diseases, say researchers at the University of Pittsburgh Graduate School of Public Health in a study published on Feb. 5 in the online ...

Genetic variation may lead to early cardiovascular disease

Jan 03, 2009

Researchers from Duke University Medical Center have identified a variation in a particular gene that increases susceptibility to early coronary artery disease. For years, scientists have known that the devastating, early-onset ...

Recommended for you

Changes in scores of genes contribute to autism risk

Oct 29, 2014

Small differences in as many as a thousand genes contribute to risk for autism, according to a study led by Mount Sinai researchers and the Autism Sequencing Consortium (ASC), and published today in the journal Nature.

Dozens of genes associated with autism in new research

Oct 29, 2014

Two major genetic studies of autism, led in part by UC San Francisco scientists and involving more than 50 laboratories worldwide, have newly implicated dozens of genes in the disorder. The research shows ...

Genetic link to kidney stones identified

Oct 29, 2014

A new breakthrough could help kidney stone sufferers get an exact diagnosis and specific treatment after genetic links to the condition were identified.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.