NEW YORK (GenomeWeb) – An international research team, led by the University of Cambridge, has discovered 15 new risk loci for coronary artery disease (CAD).
The study, published today in Nature Genetics, adds to the 58 known risk loci for the disease and sheds light on the mechanisms responsible for disease progression. These 15 new risk loci bring the total number of known risk loci associated with CAD to 73.
"Coronary artery disease is a leading cause of morbidity and mortality worldwide," the researchers wrote. "Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification."
The team collected samples from 56,309 participants from European (approximately 52 percent), South Asian (approximately 23 percent), East Asian (approximately 17 percent), and African American (approximately 8 percent) ancestry. They then genotyped the samples using Illumina's CardioMetabochip array. The researchers also performed a meta-analysis of results with 194,427 previously genotyped participants (88,192 CAD cases and 162,544 controls) made up of participants from a European ancestry study, and another from all four ancestry groups. They cross-referenced gene expression profiles with expression quantitative trait locus databases, including GTEx, MuTHER, and STARNET.
"We identified 25 new SNP-CAD association from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis, coagulation and inflammation, and vascular smooth muscle cell differentiation," they wrote.
Of these 15 loci, six have been previously associated with known CAD risk factors, such as major lipids (PCNX3, C12orf43-HNF1A, SCARB1, and DHX28) and blood pressure (GOSR2 and PROCR). Five others have previously been associated with genes that encode proteins in smooth muscle cells (LMOD1, SERPINH1, DDX59-CAMSAP2, TNS1, and PECAM1).
The researchers also noted that aside from implicating atherosclerosis and traditional risk factors as mechanisms in the pathobiology of CAD, the findings "highlight the potential importance of biological processes active in the arterial wall involving endothelial, smooth muscle, and white blood cells, and promote coronary atherogenesis."