Genome-wide association study of coronary and aortic calcification implicates risk loci for coronary artery disease and myocardial infarction

Abstract

Arterial calcification is a well-known risk factor for coronary artery disease (CAD) and myocardial infarction (MI). We performed a genome-wide association study on coronary artery calcification and aortic calcification as intermediate traits for CAD/MI. We tested ∼2.5 million SNPs for association with coronary artery calcification and aortic calcification in 2620 male individuals of the NELSON trial, who underwent chest CT scans. All participants were current or former heavy smokers. No SNPs were associated with aortic calcification on a genome-wide scale. The 9p21 locus was significantly associated with coronary artery calcification (rs1537370, P = 2.3 × 10−11). Since this locus corresponds to the strongest SNP association for CAD/MI, we tested 24 published and validated CAD/MI risk SNPs for association with arterial calcification. Besides the CAD/MI SNP at 9p21 (rs4977574, P = 3.1 × 10−10), two additional loci at ADAMTS7 (rs3825807, P = 6.5 × 10−6) and at PHACTR1 (rs12526453, P = 1.0 × 10−3) show a nominally significant association with coronary artery calcification with MI/CAD risk alleles increasing the degree of arterial calcification. The 9p21 locus was also nominally associated with aortic calcification (P = 3.2 × 10−4). These findings indicate that these CAD and MI risk loci are likely involved in arterial calcification.