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

• Published in: Atherosclerosis Vol. 228; no. 2; pp. 400 - 405
• Main Authors: van Setten, Jessica, Isgum, Ivana, Smolonska, Joanna, Ripke, Stephan, de Jong, Pim A., Oudkerk, Matthijs, de Koning, Harry, Lammers, Jan-Willem J., Zanen, Pieter, Groen, Harry J.M., Marike Boezen, H., Postma, Dirkje S., Wijmenga, Cisca, Viergever, Max A., Mali, Willem P.Th.M., de Bakker, Paul I.W.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.06.2013
• Subjects: ADAM Proteins; ADAM Proteins - genetics; ADAMTS7 Protein; adverse effects; Aged; alleles; Aortic Diseases; Aortic Diseases - diagnostic imaging; Aortic Diseases - epidemiology; Aortic Diseases - genetics; Aortography; Aortography - methods; Arteries; Atherosclerosis; calcification; Calcium; Cardiovascular; chest; Coronary Angiography; Coronary Angiography - methods; coronary artery disease; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - epidemiology; Coronary Artery Disease - genetics; coronary vessels; epidemiology; Gene Frequency; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Humans; Imaging; loci; Male; methods; Microfilament Proteins; Microfilament Proteins - genetics; Middle Aged; Multidetector Computed Tomography; myocardial infarction; Myocardial Infarction - diagnostic imaging; Myocardial Infarction - genetics; Netherlands; Netherlands - epidemiology; Phenotype; Polymorphism, Single Nucleotide; Predictive Value of Tests; Quantitative Trait Loci; Quantitative Trait, Heritable; radiography; risk; Risk Assessment; Risk Factors; single nucleotide polymorphism; Smoking; Smoking - adverse effects; Smoking - epidemiology; Vascular Calcification; Vascular Calcification - diagnostic imaging; Vascular Calcification - epidemiology; Vascular Calcification - genetics; Netherlands; Genetics; Calcium; Imaging; Arteries; Atherosclerosis
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2013.02.039

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. •We performed a GWAS of coronary artery and aorta calcification in a smokers cohort.•The 9p21 locus was significantly associated with coronary and aorta calcification.•We tested 24 SNPs CAD/MI risk SNPs for association with calcification.•3 loci (9p21, ADAMTS7, PHACTR1) are associated with arterial calcification.•These loci give insight into causal role of calcification in CAD/MI.