title: Common sequence variants associated with coronary artery disease correlate with the extent of coronary atherosclerosis.
abstract: OBJECTIVE
  Single-nucleotide polymorphisms predisposing to coronary artery disease (CAD) have been shown to predict cardiovascular risk in healthy individuals when combined into a genetic risk score (GRS). We examined whether the cumulative burden of known genetic risk variants associated with risk of CAD influences the development and progression of coronary atherosclerosis.
  
  
  RESULTS
  We investigated the combined effects of all known CAD variants in a cross-sectional study of 8622 Icelandic patients with angiographically significant CAD (≥ 50% diameter stenosis). We constructed a GRS based on 50 CAD variants and tested for association with the number of diseased coronary arteries on angiography. In models adjusted for traditional cardiovascular risk factors, the GRS associated significantly with CAD extent (difference per SD increase in GRS, 0.076; P=7.3 × 10(-17)). When compared with the bottom GRS quintile, patients in the top GRS quintile were roughly 1.67× more likely to have multivessel disease (odds ratio, 1.67; 95% confidence interval, 1.45-1.94). The GRS significantly improved prediction of multivessel disease over traditional cardiovascular risk factors (χ(2) likelihood ratio 48.1; P<0.0001) and modestly improved discrimination, as estimated by the C-statistic (without GRS versus with GRS, 64.0% versus 64.8%) and the integrated discrimination improvement (0.52%). Furthermore, the GRS associated with an earlier age at diagnosis of angiographic CAD. These findings were replicated in an independent sample from the Emory Biobank study (n=1853).
  
  
  CONCLUSIONS
  When combined into a single GRS, known genetic risk variants for CAD contribute significantly to the extent of coronary atherosclerosis in patients with significant angiographic disease.
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.).
authors.forename: Eythor
authors.initials: E
authors.lastname: Bjornsson
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.).
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.).
authors.forename: Anna
authors.initials: A
authors.lastname: Helgadottir
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.).
authors.forename: Thorarinn
authors.initials: T
authors.lastname: Gudnason
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.).
authors.forename: Tomas
authors.initials: T
authors.lastname: Gudbjartsson
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.).
authors.forename: Kristjan
authors.initials: K
authors.lastname: Eyjolfsson
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.).
authors.forename: Riyaz S
authors.initials: RS
authors.lastname: Patel
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.).
authors.forename: Nima
authors.initials: N
authors.lastname: Ghasemzadeh
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.).
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.).
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.).
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.).
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Thorgeirsson
authors.affiliation: From the Faculty of Medicine (E.B., A.H., T.G., U.T., G.T., K.S.) and Department of Engineering and Natural Sciences (D.F.G.), University of Iceland, Reykjavik, Iceland; deCODE Genetics, Reykjavik, Iceland (E.B., D.F.G., A.H., G.T., U.T., K.S.); Department of Medicine (T.G., K.E., G.T.), and Department of Surgery (T.G.), Landspitali University Hospital, Reykjavik, Iceland; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (R.S.P., N.G., A.A.Q.); and Institute of Cardiovascular Sciences, University College London, London, United Kingdom (R.S.P.). kstefans@decode.is.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000367:Age Factors; D000368:Aged; D053241:Apoprotein(a) / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011859:Radiography
chemical_list: D053241:Apoprotein(a)
keywords: atherosclerosis; coronary disease; genetics