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

TitleGenome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium.
Publication TypeJournal Article
Year of Publication2016
AuthorsDehghan A, Bis JC, White CC, Smith A V, Morrison AC, L Cupples A, Trompet S, Chasman DI, Lumley T, Völker U, Buckley BM, Ding J, Jensen MK, Folsom AR, Kritchevsky SB, Girman CJ, Ford I, Dörr M, Salomaa V, Uitterlinden AG, Eiriksdottir G, Vasan RS, Franceschini N, Carty CL, Virtamo J, Demissie S, Amouyel P, Arveiler D, Heckbert SR, Ferrières J, Ducimetière P, Smith NL, Wang YA, Siscovick DS, Rice KM, Wiklund P-G, Taylor KD, Evans A, Kee F, Rotter JI, Karvanen J, Kuulasmaa K, Heiss G, Kraft P, Launer LJ, Hofman A, Markus MRP, Rose LM, Silander K, Wagner P, Benjamin EJ, Lohman K, Stott DJ, Rivadeneira F, Harris TB, Levy D, Liu Y, Rimm EB, J Jukema W, Völzke H, Ridker PM, Blankenberg S, Franco OH, Gudnason V, Psaty BM, Boerwinkle E
Secondary AuthorsO'Donnell CJ
JournalPLoS One
Date Published2016
KeywordsAged, Cohort Studies, Cooperative Behavior, Coronary Artery Disease, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Myocardial Infarction, Polymorphism, Single Nucleotide, Prospective Studies

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 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.

RESULTS: In 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

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.

Alternate JournalPLoS One
PubMed ID26950853
PubMed Central IDPMC4780701
Grant ListR01 HL120393 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States