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Meta-Analysis
. 2011 Dec 20;124(25):2855-64.
doi: 10.1161/CIRCULATIONAHA.110.974899. Epub 2011 Dec 5.

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

Christopher J O'Donnell  1 , Maryam Kavousi, Albert V Smith, Sharon L R Kardia, Mary F Feitosa, Shih-Jen Hwang, Yan V Sun, Michael A Province, Thor Aspelund, Abbas Dehghan, Udo Hoffmann, Lawrence F Bielak, Qunyuan Zhang, Gudny Eiriksdottir, Cornelia M van Duijn, Caroline S Fox, Mariza de Andrade, Aldi T Kraja, Sigurdur Sigurdsson, Suzette E Elias-Smale, Joanne M Murabito, Lenore J Launer, Aad van der Lugt, Sekar Kathiresan; CARDIoGRAM Consortium; Gabriel P Krestin, David M Herrington, Timothy D Howard, Yongmei Liu, Wendy Post, Braxton D Mitchell, Jeffrey R O'Connell, Haiqing Shen, Alan R Shuldiner, David Altshuler, Roberto Elosua, Veikko Salomaa, Stephen M Schwartz, David S Siscovick, Benjamin F Voight, Joshua C Bis, Nicole L Glazer, Bruce M Psaty, Eric Boerwinkle, Gerardo Heiss, Stefan Blankenberg, Tanja Zeller, Philipp S Wild, Renate B Schnabel, Arne Schillert, Andreas Ziegler, Thomas F Münzel, Charles C White, Jerome I Rotter, Michael Nalls, Matthijs Oudkerk, Andrew D Johnson, Anne B Newman, Andre G Uitterlinden, Joseph M Massaro, Julie Cunningham, Tamara B Harris, Albert Hofman, Patricia A Peyser, Ingrid B Borecki, L Adrienne Cupples, Vilmundur Gudnason, Jacqueline C M Witteman
Collaborators, Affiliations
Meta-Analysis

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

Christopher J O'Donnell et al. Circulation. .

Abstract

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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Conflict of interest statement

Disclosures: Dr. Ziegler reports receiving honoraria and ownership interest >$10K. Dr’s. Rotter, Murabito, Borecki, Bielack, Kardia, and Witteman report receiving government research grants relevant to the research topic. No other co-author has reported a conflict.

Figures

Figure 1
Figure 1
Plot of –log10(P) for association of SNPs and chromosomal position for all autosomal SNPs analyzed in the age and sex-adjusted model of CAC quantity in the meta-analysis of five independent discovery cohorts.
Figure 2
Figure 2
Observed –log(P) and recombination rates by chromosomal position for all associated SNPs nearby (a) rs1333049 near CDKN2B on 9p21.3 and (b) rs9349379 near PHACTR on 6p24. Results from the genome-wide association analysis of SNPs versus age and sex-adjusted CAC quantity in the meta-analysis of five independent discovery cohorts. Association plots were conducted using SNAP.[27] Top SNPs of interest and P values in each region are indicated (blue diamonds). Color coding indicates the strength of LD of each SNP with the top SNP in each region: red (r2≥0.08), orange (r2≥0.5), yellow (r2≥0.2), white with no color (r2<0.2).
Figure 2
Figure 2
Observed –log(P) and recombination rates by chromosomal position for all associated SNPs nearby (a) rs1333049 near CDKN2B on 9p21.3 and (b) rs9349379 near PHACTR on 6p24. Results from the genome-wide association analysis of SNPs versus age and sex-adjusted CAC quantity in the meta-analysis of five independent discovery cohorts. Association plots were conducted using SNAP.[27] Top SNPs of interest and P values in each region are indicated (blue diamonds). Color coding indicates the strength of LD of each SNP with the top SNP in each region: red (r2≥0.08), orange (r2≥0.5), yellow (r2≥0.2), white with no color (r2<0.2).
See this image and copyright information in PMC

References

    1. Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008;117:e25–e146. - PubMed
    1. Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM, Lauer MS, Post WS, Raggi P, Redberg RF, Rodgers GP, Shaw LJ, Taylor AJ, Weintraub WS, Harrington RA, Abrams J, Anderson JL, Bates ER, Grines CL, Hlatky MA, Lichtenberg RC, Lindner JR, Pohost GM, Schofield RS, Shubrooks SJ, Jr, Stein JH, Tracy CM, Vogel RA, Wesley DJ. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) Circulation. 2007;115:402–426. - PubMed
    1. Peyser PA, Bielak LF, Chu JS, Turner ST, Ellsworth DL, Boerwinkle E, Sheedy PF. Heritability of coronary artery calcium quantity measured by electron beam computed tomography in asymptomatic adults. Circulation. 2002;106:304–308. - PubMed
    1. Parikh NI, Hwang SJ, Larson MG, Cupples LA, Fox CS, Manders ES, Murabito JM, Massaro JM, Hoffmann U, O'Donnell CJ. Parental occurrence of premature cardiovascular disease predicts increased coronary artery and abdominal aortic calcification in the Framingham Offspring and Third Generation cohorts. Circulation. 2007;116:1473–1481. - PubMed
    1. O'Rourke RA, Brundage BH, Froelicher VF, Greenland P, Grundy SM, Hachamovitch R, Pohost GM, Shaw LJ, Weintraub WS, Winters WL., Jr American College of Cardiology/American Heart Association Expert Consensus Document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. J Am Coll Cardiol. 2000;36:326–340. - PubMed

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