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

Publication ,  Journal Article
Dehghan, A; Bis, JC; White, CC; Smith, AV; Morrison, AC; Cupples, LA; Trompet, S; Chasman, DI; Lumley, T; Völker, U; Buckley, BM; Ding, J ...
Published in: PLoS One
2016

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<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). 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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

3

Start / End Page

e0144997

Location

United States

Related Subject Headings

  • Prospective Studies
  • Polymorphism, Single Nucleotide
  • Myocardial Infarction
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • General Science & Technology
  • Female
 

Citation

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Chicago
ICMJE
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Dehghan, A., Bis, J. C., White, C. C., Smith, A. V., Morrison, A. C., Cupples, L. A., … 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, 11(3), e0144997. https://doi.org/10.1371/journal.pone.0144997
Dehghan, Abbas, Joshua C. Bis, Charles C. White, Albert Vernon Smith, Alanna C. Morrison, L Adrienne Cupples, Stella Trompet, et al. “Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium.PLoS One 11, no. 3 (2016): e0144997. https://doi.org/10.1371/journal.pone.0144997.
Dehghan A, Bis JC, White CC, Smith AV, Morrison AC, Cupples LA, et al. Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium. PLoS One. 2016;11(3):e0144997.
Dehghan, Abbas, et al. “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, 2016, p. e0144997. Pubmed, doi:10.1371/journal.pone.0144997.
Dehghan A, Bis JC, White CC, Smith AV, Morrison AC, Cupples LA, 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, Jukema JW, Völzke H, Ridker PM, Blankenberg S, Franco OH, Gudnason V, Psaty BM, Boerwinkle E, O’Donnell CJ. Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium. PLoS One. 2016;11(3):e0144997.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

3

Start / End Page

e0144997

Location

United States

Related Subject Headings

  • Prospective Studies
  • Polymorphism, Single Nucleotide
  • Myocardial Infarction
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • General Science & Technology
  • Female