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O'Donnell, C.J.* ; Kavousi, M.* ; Smith, A.V.* ; Kardia, S.L.* ; Feitosa, M.F.* ; Hwang, S.J.* ; Sun, Y.V.* ; Province, M.A.* ; Aspelund, T.* ; Dehghan, A.* ; Hoffmann, U.* ; Bielak, L.F.* ; Zhang, Q.* ; Eiriksdottir, G.* ; van Duijn, C.M.* ; Fox, C.S.* ; de Andrade, M.* ; Kraja, A.T.* ; Sigurdsson, S.* ; Elias-Smale, S.E.* ; Murabito, J.M.* ; Launer, L.J.* ; van der Lugt, A.* ; Kathiresan, S.* ; CARDIoGRAM Consortium (Döring, A. ; Wichmann, H.-E. ; Illig, T. ; Klopp, N. ; Meisinger, C. ; Meitinger, T. ; Peters, A.) ; Krestin, G.P.* ; Herrington, D.M.* ; Howard, T.D.* ; Liu, Y.* ; Post, W.* ; Mitchell, B.D.* ; O'Connell, J.R.* ; Shen, H.* ; Shuldiner, A.R.* ; Altshuler, D.* ; Elosua, R.* ; Salomaa, V.* ; Schwartz, S.M.* ; Siscovick, D.S.* ; Voight, B.F.* ; Bis, J.C.* ; Glazer, N.L.* ; Psaty, B.M.* ; Boerwinkle, E.* ; Heiss, G.* ; Blankenberg, S.* ; Zeller, T.* ; Wild, P.S.* ; Schnabel, R.B.* ; Schillert, A.* ; Ziegler, A.* ; Munzel, T.F.* ; White, C.C.* ; Rotter, J.I.* ; Nalls, M.* ; Oudkerk, M.* ; Johnson, A.D.* ; Newman, A.B.* ; Uitterlinden, A.G.* ; Massaro, J.M.* ; Cunningham, J.* ; Harris, T.B.* ; Hofman, A.* ; Peyser, P.A.* ; Borecki, I.B.* ; Cupples, L.A.* ; Gudnason, V.* ; Witteman, J.C.*

Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.

Circulation 124, 2855-2864 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
BACKGROUND: Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI. METHODS AND RESULTS: Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P=7.58×10(-19)) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P=2.65×10(-11)) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene). CONCLUSIONS: SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords cardiac computed tomography; coronary artery calcification; coronary atherosclerosis; genome-wide association studies; myocardial infarction; BEAM COMPUTED-TOMOGRAPHY; EXPERT CONSENSUS DOCUMENT; ABDOMINAL AORTIC-ANEURYSM; BONE-MINERAL DENSITY; OLD-ORDER AMISH; AMERICAN-COLLEGE; SEQUENCE VARIANT; BLOOD-PRESSURE; HEART-DISEASE; RISK
ISSN (print) / ISBN 0009-7322
e-ISSN 1524-4539
Journal Circulation
Quellenangaben Volume: 124, Issue: 25, Pages: 2855-2864 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
Research Unit Molecular Epidemiology (AME)