Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium
Creators: name: Jukema, J. Wouter
name: Harris, Tamara B.
name: Jensen, Majken K.
name: Eiriksdottir, Gudny
name: Vasan, Ramachandran S.
name: Blankenberg, Stefan
name: Ridker, Paul M.
name: Taylor, Kent D.
name: Smith, Albert Vernon
name: Rose, Lynda M.
name: Stott, David J.
name: Heckbert, Susan R.
name: Psaty, Bruce M.
name: Rice, Kenneth M.
name: Amouyel, Philippe
name: Trompet, Stella
name: Girman, Cynthia J.
name: Karvanen, Juha
name: Volzke, Henry
name: Rimm, Eric B.
name: Kuulasmaa, Kari
name: Kritchevsky, Stephen B.
name: Siscovick, David S.
name: Arveiler, Dominique
name: Rivadeneira, Fernando
name: Liu, Yongmei
name: Dehghan, Abbas
name: Wiklund, Per-Gunnar
name: Carty, Cara L.
name: Kee, Frank
name: Uitterlinden, Andre G.
name: Dorr, Marcus
name: Benjamin, Emelia J.
name: Kraft, Peter
name: Franceschini, Nora
name: Ducimetiere, Pierre
name: Ferrieres, Jean
name: Salomaa, Veikko
name: Hofman, Albert
name: Chasman, Daniel I.
name: Cupples, L. Adrienne
name: Levy, Daniel
name: Virtamo, Jarmo
name: Morrison, Alanna C.
name: Evans, Alun
name: Gudnason, Vilmundur
name: Lumley, Thomas
name: Ding, Jingzhong
name: White, Charles C.
name: Wagner, Peter
name: Smith, Nicholas L.
name: Silander, Kaisa
name: Rotter, Jerome I.
name: Heiss, Gerardo
name: Buckley, Brendan M.
name: Folsom, Aaron R.
name: Boerwinkle, Eric
name: Ford, Ian
name: Demissie, Serkalem
name: Launer, Lenore J.
name: Franco, Oscar H.
name: Bis, Joshua C.
name: Volker, Uwe
name: Markus, Marcello R.P.
name: Wang, Ying A.
name: O'Donnell, Christopher J.
name: Lohman, Kurt
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2016

description: BackgroundData 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.MethodsWe 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 5×10−6 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.ResultsIn Stage I 15 loci passed the threshold of 5×10−6; 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<8.8×10−3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10−9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10−3).ConclusionsQKI 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.