Scientists at deCODE Genetics and academic colleagues from the U.S. identified a common genetic variant that confers increased risk of heart attacks. The variant, a SNP on chromosome 9p21, was discovered through genome-wide SNP analysis in Iceland and replicated in three cohorts of European descent from Philadelphia, Atlanta, and Durham, NC.
Of more than 17,000 patients and control subjects in the study, more than 20% of participants carried two copies of the variant, which corresponded to an increased risk of more than 60%. Moreover, in early onset cases—men and women who suffered a heart attack before the ages of 50 and 60, respectively—two copies of the variant meant an approximate doubling of risk.
deCODE scientists began the study by genotyping a large group of Icelandic heart patients and controls with the Illumina HumanHap300 gene chip, which captures more than 300,000 SNPs across the genome. This analysis yielded several markers significantly associated with the disease. The deCODE team then utilized data from the international HapMap project to identify additional SNPs not on the gene chip but which correlated with those identified in the first analysis.
This yielded a SNP, called rs10757278, with the highest association to the disease and which was replicated in all of the cohorts. This SNP lies within a block of the genome containing two well know tumor suppressor genes, CDKN2A and CDKN2B. The proteins encoded by these genes are also involved in cell proliferation, cell aging, and apoptosis.
deCODE plans to bundle this discovery with other genetic variants it has linked to risk of heart attack into a DNA-based test for gauging inherited risk of heart attacks.
The paper is published in the online edition of Science.