The largest study ever completed of genetic factors associated with heart attacks has identified nine genetic regions, three of which are new, that appear to increase the risk for early-onset myocardial infarction. One of those new regions had been found previously to promote the buildup of atherosclerotic plaque in the coronary arteries.
The report from the Myocardial Infarction Genetics Consortium is derived from testing completed on 26,000 individuals—a total of 13,000 heart attack patients and 13,000 controls—in 10 different countries.
“For several decades it has been known that the risk for heart attack clusters in families and that some of this familial clustering is due to differences in DNA sequence,” said Sekar Kathiresan, M.D., director of preventive cardiology at Massachusetts General Hospital. “We set out to find specific, single-letter differences in the genome that may be responsible for an increased familial risk for heart attack.”
The team used the International Haplotype Map, genotyping arrays, and a gene chip developed by one researcher’s team that can simulaneously screen for SNPs and copy-number variants, deletions, or duplications of gene segments. 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.
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 researchers acknowledge that the increased risk associated with individual SNPs is minor, facts 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 Dr. Kathiresan.
“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.”
The report appeared in the early online release of Nature Genetics on February 8.