Published in
Public Library of Science, PLoS ONE, 3(11), p. e0144997, 2016
DOI: 10.1371/journal.pone.0144997
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Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium
,
Joshua C. Bis,
Charles C. White,
Albert Vernon Smith ,
Alanna C. Morrison,
L. Adrienne Cupples ,
Stella Trompet,
Daniel I. Chasman,
Thomas Lumley,
Uwe Völker,
Brendan M. Buckley,
Jingzhong Ding,
Majken K. Jensen,
Aaron R. Folsom,
Stephen B. Kritchevsky
and other authors.
Full text: Download
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 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