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

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Dehghan, Abbas
    • Other Affiliation: Department of Epidemiology; Erasmus University Medical Center
  • Bis, Joshua C.
    • Other Affiliation: Cardiovascular Health Research Unit; Department of Medicine; University of Washington
  • White, Charles C.
    • Other Affiliation: Department of Biostatistics; Boston University School of Public Health
  • Smith, Albert Vernon
    • Other Affiliation: University of Iceland
  • Morrison, Alanna C.
    • Other Affiliation: Human Genetics Center; Division of Epidemiology; Human Genetics; and Environmental Sciences; University of Texas Health Science Center at Houston
  • Cupples, L. Adrienne
    • Other Affiliation: Department of Biostatistics; Boston University School of Public Health
  • Trompet, Stella
    • Other Affiliation: Department of Cardiology; Leiden University Medical Center
  • Chasman, Daniel I.
    • Other Affiliation: Division of Preventive Medicine; Brigham and Women's Hospital; Harvard Medical School
  • Lumley, Thomas
    • Other Affiliation: Department of Statistics; University of Auckland
  • Volker, Uwe
    • Other Affiliation: Interfaculty Institute for Genetics and Functional Genomics; University Medicine Greifswald
  • Buckley, Brendan M.
    • Other Affiliation: Department of Pharmacology and Therapeutics; University College
  • Ding, Jingzhong
    • Other Affiliation: Department of Internal Medicine; Division of Geriatrics; Wake Forest University
  • Jensen, Majken K.
    • Other Affiliation: Department of Nutrition; Harvard School of Public Health
  • Folsom, Aaron R.
    • Other Affiliation: Division of Epidemiology and Community Health; School of Public Health; University of Minnesota
  • Kritchevsky, Stephen B.
    • Other Affiliation: Sticht Center on Aging; Wake Forest School of Medicine
  • Girman, Cynthia J.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
    • Other Affiliation: Department of Epidemiology; Merck Research Laboratories; Merck Sharp and Dohme Corp.
  • Ford, Ian
    • Other Affiliation: Robertson Centre for Biostatistics; University of Glasgow
  • Dorr, Marcus
    • Other Affiliation: DZHK (German Center for Cardiovascular Research); Partner Site
  • Salomaa, Veikko
    • Other Affiliation: National Institute for Health and Welfare
  • Uitterlinden, Andre G.
    • Other Affiliation: Department of Epidemiology; Erasmus University Medical Center
  • Eiriksdottir, Gudny
    • Other Affiliation: Icelandic Heart Association
  • Vasan, Ramachandran S.
    • Other Affiliation: Department of Preventive Medicine; Boston University School of Medicine
  • Franceschini, Nora
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Carty, Cara L.
    • Other Affiliation: Public Health Sciences; Fred Hutchinson Cancer Research Center
  • Virtamo, Jarmo
    • Other Affiliation: National Institute for Health and Welfare
  • Demissie, Serkalem
    • Other Affiliation: Department of Biostatistics; Boston University School of Public Health
  • Amouyel, Philippe
    • Other Affiliation: Department of Epidemiology and Public Health; Pasteur Institute of Lille
  • Arveiler, Dominique
    • Other Affiliation: Department of Epidemiology and Public Health; EA; 3430; University of Strasbourg
  • Heckbert, Susan R.
    • Other Affiliation: Group Health Research Institute; Group Health Cooperative
  • Ferrieres, Jean
    • Other Affiliation: Departments of Cardiology and Epidemiology; Toulouse University Hospital
  • Ducimetiere, Pierre
    • Other Affiliation: National Institute of Health and Medical Research (U258)
  • Smith, Nicholas L.
    • Other Affiliation: Seattle Epidemiologic Research and Information Center; Department of Veterans Affairs Office of Research and Development
  • Wang, Ying A.
    • Other Affiliation: Department of Biostatistics; Boston University School of Public Health
  • Siscovick, David S.
    • Other Affiliation: New York Academy of Medicine
  • Rice, Kenneth M.
    • Other Affiliation: Department of Biostatistics; University of Washington
  • Wiklund, Per-Gunnar
    • Other Affiliation: Department of Medicine; Umeå University Hospital
  • Taylor, Kent D.
    • Other Affiliation: Institute for Translational Genomics and Population Sciences; Los Angeles Biomedical Research Institute
  • Evans, Alun
    • Other Affiliation: UKCRC Centre of Excellence for Public Health Research (Northern Ireland); Queen's University of Belfast
  • Kee, Frank
    • Other Affiliation: UKCRC Centre of Excellence for Public Health Research (Northern Ireland); Queen's University of Belfast
  • Rotter, Jerome I.
    • Other Affiliation: Institute for Translational Genomics and Population Sciences; Los Angeles Biomedical Research Institute
  • Karvanen, Juha
    • Other Affiliation: Department of Mathematics and Statistics; University of Jyväskylä
  • Kuulasmaa, Kari
    • Other Affiliation: National Institute for Health and Welfare
  • Heiss, Gerardo
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Kraft, Peter
    • Other Affiliation: Department of Epidemiology; Harvard School of Public Health
  • Launer, Lenore J.
    • Other Affiliation: Laboratory of Epidemiology; Demography; and Biometry; National Institute on Aging; National Institutes of Health
  • Hofman, Albert
    • Other Affiliation: Department of Epidemiology; Erasmus University Medical Center
  • Markus, Marcello R.P.
    • Other Affiliation: DZHK (German Center for Cardiovascular Research); Partner Site
  • Rose, Lynda M.
    • Other Affiliation: Division of Preventive Medicine; Brigham and Women's Hospital; Harvard Medical School
  • Silander, Kaisa
    • Other Affiliation: Institute for Molecular Medicine FIMM; University of Helsinki
  • Wagner, Peter
    • Other Affiliation: Institute for Molecular Medicine FIMM; University of Helsinki
  • Benjamin, Emelia J.
    • Other Affiliation: Section of Cardiovascular Medicine; Department of Medicine; Boston University School of Medicine
  • Lohman, Kurt
    • Other Affiliation: Department of Epidemiology and Prevention; Public Health Sciences; Wake Forest School of Medicine
  • Stott, David J.
    • Other Affiliation: Institute of Cardiovascular and Medical Sciences; Faculty of Medicine; University of Glasgow
  • Rivadeneira, Fernando
    • Other Affiliation: Department of Epidemiology; Erasmus University Medical Center
  • Harris, Tamara B.
    • Other Affiliation: Laboratory of Epidemiology; Demography; and Biometry; National Institute on Aging; National Institutes of Health
  • Levy, Daniel
    • Other Affiliation: Boston University's and National Heart Lung; Blood Institute's Framingham Heart Study
  • Liu, Yongmei
    • Other Affiliation: Department of Epidemiology and Prevention; Public Health Sciences; Wake Forest School of Medicine
  • Rimm, Eric B.
    • Other Affiliation: Department of Nutrition; Harvard School of Public Health
  • Jukema, J. Wouter
    • Other Affiliation: Durrer Center for Cardiogenetic Research
  • Volzke, Henry
    • Other Affiliation: DZHK (German Center for Cardiovascular Research); Partner Site
  • Ridker, Paul M.
    • Other Affiliation: Division of Preventive Medicine; Brigham and Women's Hospital; Harvard Medical School
  • Blankenberg, Stefan
    • Other Affiliation: Department of General and Interventional Cardiology; University Heart Center Hamburg-Eppendorf
  • Franco, Oscar H.
    • Other Affiliation: Department of Epidemiology; Erasmus University Medical Center
  • Gudnason, Vilmundur
    • Other Affiliation: University of Iceland
  • Psaty, Bruce M.
    • Other Affiliation: Group Health Research Institute; Group Health Cooperative
  • Boerwinkle, Eric
    • Other Affiliation: Human Genetics Center; Division of Epidemiology; Human Genetics; and Environmental Sciences; University of Texas Health Science Center at Houston
  • O'Donnell, Christopher J.
    • Other Affiliation: Boston University's and National Heart Lung; Blood Institute's Framingham Heart Study
Abstract
  • 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.
Date of publication
Keyword
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • PloS One
Journal volume
  • 11
Journal issue
  • 3
Page start
  • e0144997
Language
  • English
ISSN
  • 1932-6203

Relations

Parents:

This work has no parents.

In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details PubMedCentral-PMC4780701.pdf 2016 Public Download