Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies : The CHARGE Consortium

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Dehghan , A , Bis , J C , White , C C , Smith , A V , Morrison , A C , Cupples , L A , Trompet , S , Chasman , D I , Lumley , T , Voelker , U , Buckley , B M , Ding , J , Jensen , M K , Folsom , A R , Kritchevsky , S B , Girman , C J , Ford , I , Doerr , M , Salomaa , V , Uitterlinden , A G , Eiriksdottir , G , Vasan , R S , Franceschini , N , Carty , C L , Virtamo , J , Demissie , S , Amouyel , P , Arveiler , D , Heckbert , S R , Ferrieres , J , Ducimetiere , P , Smith , N L , Wang , Y A , Siscovick , D S , Rice , K M , Wiklund , P-G , Taylor , K D , Evans , A , Kee , F , Rotter , J I , Karvanen , J , Kuulasmaa , K , Heiss , G , Kraft , P , Launer , L J , Hofman , A , Markus , M R P , Rose , L M , Silander , K , Wagner , P , Benjamin , E J , Lohman , K , Stott , D J , Rivadeneira , F , Harris , T B , Levy , D , Liu , Y , Rimm , E B , Jukema , J W , Voelzke , H , Ridker , P M , Blankenberg , S , Franco , O H , Gudnason , V , Psaty , B M , Boerwinkle , E & O'Donnell , C J 2016 , ' Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies : The CHARGE Consortium ' PLoS One , vol. 11 , no. 3 , 0144997 . DOI: 10.1371/journal.pone.0144997

Title: Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies : The CHARGE Consortium
Author: Dehghan, Abbas; Bis, Joshua C.; White, Charles C.; Smith, Albert Vernon; Morrison, Alanna C.; Cupples, L. Adrienne; Trompet, Stella; Chasman, Daniel I.; Lumley, Thomas; Voelker, Uwe; Buckley, Brendan M.; Ding, Jingzhong; Jensen, Majken K.; Folsom, Aaron R.; Kritchevsky, Stephen B.; Girman, Cynthia J.; Ford, Ian; Doerr, Marcus; Salomaa, Veikko; Uitterlinden, Andre G.; Eiriksdottir, Gudny; Vasan, Ramachandran S.; Franceschini, Nora; Carty, Cara L.; Virtamo, Jarmo; Demissie, Serkalem; Amouyel, Philippe; Arveiler, Dominique; Heckbert, Susan R.; Ferrieres, Jean; Ducimetiere, Pierre; Smith, Nicholas L.; Wang, Ying A.; Siscovick, David S.; Rice, Kenneth M.; Wiklund, Per-Gunnar; Taylor, Kent D.; Evans, Alun; Kee, Frank; Rotter, Jerome I.; Karvanen, Juha; Kuulasmaa, Kari; Heiss, Gerardo; Kraft, Peter; Launer, Lenore J.; Hofman, Albert; Markus, Marcello R. P.; Rose, Lynda M.; Silander, Kaisa; Wagner, Peter; Benjamin, Emelia J.; Lohman, Kurt; Stott, David J.; Rivadeneira, Fernando; Harris, Tamara B.; Levy, Daniel; Liu, Yongmei; Rimm, Eric B.; Jukema, J. Wouter; Voelzke, Henry; Ridker, Paul M.; Blankenberg, Stefan; Franco, Oscar H.; Gudnason, Vilmundur; Psaty, Bruce M.; Boerwinkle, Eric; O'Donnell, Christopher J.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
Date: 2016-03-07
Language: eng
Number of pages: 16
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/161149
Abstract: Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5x10(-6) in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5x10(-6); 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.
Subject: CARDIOVASCULAR-DISEASE
CHROMOSOME 9P21
RISK
DESIGN
METAANALYSIS
SUSCEPTIBILITY
PREDICTION
ROTTERDAM
3111 Biomedicine
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