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Circulation. 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.

Collaborators (173)

Kathiresan S, Reilly MP, Samani NJ, Schunkert H, Assimes TL, Boerwinkle E, Erdmann J, Hall A, Hengstenberg C, Kathiresan S, König IR, Reilly MP, Samani NJ, Thompson JR, Thorsteinsdottir U, Ziegler A, König IR, Thompson JR, Absher D, Chen L, Cupples LA, Halperin E, Li M, Musunuru K, Schillert A, Thorleifsson G, Voight BF, Wells GA, Assimes TL, Deloukas P, Erdmann J, Kathiresan S, König IR, Reilly MP, Roberts R, Samani NJ, Schunkert H, Stewart AF, Absher D, Assimes TL, Fortmann S, Go A, Hlatky M, Iribarren C, Myers R, Quertermous T, Risch N, Blankenberg S, Zeller T, Schillert A, Schnabel R, Lackner K, Tiret L, Cambien F, Rupprecht HJ, Perret C, Münzel T, Bis J, Boerwinkle E, Yii I, Chen D, Adrienne L, Dehghan A, Demissie-Banjaw S, Folsom A, Gudnason V, Harris T, Heckbert S, Levy D, Marciante K, Morrison A, Psaty M, Rice K, Rotter JI, Siscovick DS, Smith N, Taylor KD, van Duijn C, Volcik K, Whitteman J, Ramachandran V, Hofman A, Uitterlinden A, Gretarsdottir S, Gulcher JR, Holm H, Kong A, Stefansson K, Thorgeirsson G, Andersen K, Thorsteinsdottir U, Erdmann J, Fischer M, Grosshennig A, König IR, Lieb W, Linsel P, Wichmann H-, Ziegler A, Schunkert H, Bruse P, Doering A, Hengstenberg C, Illig T, Klopp N, König IR, Linsel P, Loley C, Medack A, Meisinger C, Nahrstedt J, Peters A, Preuss M, Wagner K, Wichmann H-, Willenborg C, Ziegler A, Böhm BO, Dobnig H, Grammer TB, Hoffmann MM, Kleber M, Laaksonen R, Meinitzer A, Winkelmann BR, Pilz S, Scharnagl H, Stojakovic T, Tomaschitz A, Voight BF, Musunuru K, Guiducci C, Burtt N, Gabriel SB, Siscovick DS, O'Donnell CJ, Elosua R, Salomaa V, Schwartz SM, Melander O, Altshuler D, Kathiresan S, Stewart AF, Chen L, Dandona S, Wells GA, Reilly MP, Li M, Qu L, Wilensky R, Matthai W, Hakonarson HH, Devaney J, Susan Burnett M, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Knouff CW, Waterworth DM, Walker MC, Mooser V, Epstein SE, Rader DJ, Samani NJ, Thompson JR, Braund PS, Nelson CP, Wright BJ, Balmforth AJ, Ball SG, Hall AS.

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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