Center for Applied Genomics

Coronary artery disease is the most common cause of premature death and disability in the world. The findings could, in the future, help in developing new treatments and improve prediction of CAD.

The Consortium examined 49,094 genetic variants in ~ 2,100 genes cardiovascular-related genes, in 15,596 CAD cases and 34,992 controls and replicated their principal findings in an additional 17,121 cases and 40,473 controls. The study was primarily funded by the British Heart Foundation, the National Institute for Health Research (UK), and the National Institutes of Health (US).

One of the co-authors, Brendan Keating Ph.D., who is based in the Center for Applied Genomics (CAG) at The Children's Hospital of Philadelphia, conceived and developed the cardiovascular chip. Dr. Keating added "At the time of the array design in 2006 we had very few robust signals known for CAD and myocardial infarction (MI) and there was much controversy about some of the signals published."

This low cost array allowed many groups to pool appropriately collected CAD and MI cases and controls and to analyze these datasets together. Five new genes were shown to be associated with CAD/MI and, interestingly, the majority of CAD/MI signals from previous underpowered studies were found not to be true signals. This study shows the value of large scale collaborations to identify genetic variants that may be valuable drug targets. This array has also been used for a number of other large consortium studies including type-2 diabetes, stroke, lipids and body mass index, all of which are nearing publication. Many of the samples from the studies contributing to these analyses were processed and analyzed in CAG under the directorship of Dr. Hakon Hakonarson.

Co-principal investigator Professor Nilesh Samani, (British Heart Foundation Professor of Cardiology University of Leicester, UK) said "The findings add to the growing list of genes, now over 30, that affect risk of CAD and heart attacks. The findings provide new insights into, and understanding of, the causal biological pathways that cause heart disease, and particularly highlight the role of lipids and inflammation."

Professor Hugh Watkins (co-principal investigator, British Heart Foundation Professor of Cardiovascular Medicine, University of Oxford) said "Although the effects of the new genetic variants that we have identified are individually small, in the order of 5-10% per copy, new treatments that are developed on the basis of the findings could have a much broader effect, as we have learnt, for example, with statins."

--- The full article is available free of charge at PLoS Genetics ---