The largest study ever completed of genetic factors associated with heart attacks has identified nine genetic regions – three not previously described – that appear to increase the risk for early-onset myocardial infarction.
The report from the Myocardial Infarction Genetics Consortium, based on information from a total of 26,000 inviduals in 10 countries, will appear in Nature Genetics and is receiving early online release.
"For several decades, it has been known that the risk for heart attack – the leading cause of death and disability in the U.S. – clusters in families and that some of this familial clustering is due to differences in DNA sequence," says Sekar Kathiresan, MD, director of Preventive Cardiology at Massachusetts General Hospital (MGH) and corresponding author of the Nature Genetics report. "We set out to find specific, single-letter differences in the genome, what are called single-nucleotide polomorphisms (SNPs), that may be responsible for an increased familial risk for heart attack."
Groundwork for the current study was laid more than 10 years ago when co-author Christopher O'Donnell, MD, now based at the Framingham Heart Study, began to gather data on patients treated at the MGH for early-onset heart attack – men under 50 and women under 60. Kathiresan soon joined the project, and in 2006 they formed the Myocardial Infarction Genetics Consortium along with David Altshuler, MD, PhD, of the MGH Center for Human Genetic Research and the Broad Institute of MIT and Harvard, eventually involving six groups around the world that had collected samples on a total of about 3,000 early-onset heart attack patients and 3,000 healthy controls.
The current study took advantage of several scientific tools developed over the past decade. These include the International Haplotype Map, a comprehensive map of SNPs across the genome; genotyping arrays that allow screening of hundreds of thousands of SNPs at once; and a gene chip developed by Altshuler's team that can simulaneously screen for SNPs and for copy-number variants – deletions or duplications of gene segments, a type of change associated with several disease categories. After analysis of the consortium's samples identified SNPs that could be associated with heart attack risk, the researchers ran replication screens in three independent groups of samples, resulting in a total of 13,000 heart attack patients and 13,000 controls.
Significant associations with the risk of early-onset heart attacks were found for common SNPs in nine genetic regions. Three of those associations with heart attack risk were identified for the first time; and one of the novel regions also had been found, in a separate study by O'Donnell, to promote the buildup of atherosclerotic plaque in the coronary arteries. To analyze the effect of inheriting several risk-associated SNPs, participants were assigned a genotype score, which revealed that those with the highest number of risk-associated variants had more than twice the risk of an early-onset heart attack as those with the fewest. No risk associations were identified with copy-number variants.
Although the increased risk associated with individual SNPs is small, knowledge gained from the association could prove extremely valuable. "One of the known variants we identified is at a gene called PCSK9, which was originally identified in 2003," explains Kathiresan, an assistant professor of Medicine at Harvard Medical School. "Extensive study of that gene region has led to significant insight into the biology of atherosclerosis and heart attack and to efforts to develop targeted drugs. We are optimistic that investigating the mechanics of the newly mapped variants could yield similar insights. And since we already have effective ways to reduce heart-attack risk, individuals at higher genetic risk may benefit from earlier intervention, something that needs to be tested in future studies."
Sue McGreevey | EurekAlert!
Further reports about: > DNA sequence > Genetic > Nature Immunology > SNP > Universität Harvard > atherosclerosis > coronary arteries > early heart attack > familial risk for heart attack > genetic factors > genotyping arrays > heart attack risk > heart attacks > infarction > myocardial infarction > simulaneously screen > single-nucleotide polomorphisms
A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg
Urbanization to convert 300,000 km2 of prime croplands
27.12.2016 | Mercator Research Institute on Global Commons and Climate Change (MCC) gGmbH
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction