title: 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.
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
authors.forename: Jessica
authors.initials: J
authors.lastname: van Setten
authors.forename: Ivana
authors.initials: I
authors.lastname: Isgum
authors.forename: Joanna
authors.initials: J
authors.lastname: Smolonska
authors.forename: Stephan
authors.initials: S
authors.lastname: Ripke
authors.forename: Pim A
authors.initials: PA
authors.lastname: de Jong
authors.forename: Matthijs
authors.initials: M
authors.lastname: Oudkerk
authors.forename: Harry
authors.initials: H
authors.lastname: de Koning
authors.forename: Jan-Willem J
authors.initials: JW
authors.lastname: Lammers
authors.forename: Pieter
authors.initials: P
authors.lastname: Zanen
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Max A
authors.initials: MA
authors.lastname: Viergever
authors.forename: Willem P Th M
authors.initials: WP
authors.lastname: Mali
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071118:ADAMTS7 Protein; D000368:Aged; D001018:Aortic Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D001027:Aortography / Q000379:methods; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D061330:Multidetector Computed Tomography; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D061205:Vascular Calcification / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*
chemical_list: D008840:Microfilament Proteins; C570134:PHACTR1 protein, human; D051722:ADAM Proteins; D000071118:ADAMTS7 Protein; C121534:ADAMTS7 protein, human