@article{3020669,
    title = "Genomewide Association Study of Platelet Reactivity and Cardiovascular Response in Patients Treated With Clopidogrel: A Study by the International Clopidogrel Pharmacogenomics Consortium",
    author = "Verma, S.S. and Bergmeijer, T.O. and Gong, L. and Reny, J.-L. and Lewis, J.P. and Mitchell, B.D. and Alexopoulos, D. and Aradi, D. and Altman, R.B. and Bliden, K. and Bradford, Y. and Campo, G. and Chang, K. and Cleator, J.H. and Déry, J.-P. and Dridi, N.P. and Fernandez-Cadenas, I. and Fontana, P. and Gawaz, M. and Geisler, T. and Gensini, G.F. and Giusti, B. and Gurbel, P.A. and Hochholzer, W. and Holmvang, L. and Kim, E.-Y. and Kim, H.-S. and Marcucci, R. and Montaner, J. and Backman, J.D. and Pakyz, R.E. and Roden, D.M. and Schaeffeler, E. and Schwab, M. and Shin, J.G. and Siller-Matula, J.M. and ten Berg, J.M. and Trenk, D. and Valgimigli, M. and Wallace, J. and Wen, M.-S. and Kubo, M. and Lee, M.T.M. and Whaley, R. and Winter, S. and Klein, T.E. and Shuldiner, A.R. and Ritchie, M.D. and for the ICPC Investigators",
    journal = "International Journal of Clinical Pharmacology and Therapeutics",
    year = "2020",
    volume = "108",
    number = "5",
    pages = "1067-1077",
    publisher = "Nature Publishing Group",
    issn = "0946-1965",
    doi = "10.1002/cpt.1911",
    keywords = "adenosine diphosphate;  clopidogrel;  cytochrome P450 2C19;  DNA;  antithrombocytic agent;  clopidogrel;  CYP2C19 protein, human;  cytochrome P450 2C19, acute coronary syndrome;  adult;  allele;  Article;  cardiovascular disease;  cardiovascular response;  cerebrovascular accident;  chromosome;  clinical outcome;  coronary artery disease;  female;  gene locus;  genome-wide association study;  heart infarction;  human;  loading drug dose;  major clinical study;  male;  middle aged;  percutaneous coronary intervention;  pharmacogenomics;  phenotype;  platelet reactivity;  priority journal;  single nucleotide polymorphism;  adverse event;  aged;  blood;  cardiovascular disease;  clinical trial;  coronary artery disease;  drug effect;  genetics;  genome-wide association study;  metabolism;  mortality;  multicenter study;  percutaneous coronary intervention;  pharmacogenetic variant;  pharmacogenetics;  risk assessment;  risk factor;  single nucleotide polymorphism;  thrombocyte;  treatment outcome, Aged;  Blood Platelets;  Cardiovascular Diseases;  Clopidogrel;  Coronary Artery Disease;  Cytochrome P-450 CYP2C19;  Female;  Genome-Wide Association Study;  Humans;  Male;  Middle Aged;  Percutaneous Coronary Intervention;  Pharmacogenetics;  Pharmacogenomic Variants;  Platelet Aggregation Inhibitors;  Polymorphism, Single Nucleotide;  Risk Assessment;  Risk Factors;  Treatment Outcome",
    abstract = "Antiplatelet response to clopidogrel shows wide variation, and poor response is correlated with adverse clinical outcomes. CYP2C19 loss-of-function alleles play an important role in this response, but account for only a small proportion of variability in response to clopidogrel. An aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify other genetic determinants of clopidogrel pharmacodynamics and clinical response. A genomewide association study (GWAS) was performed using DNA from 2,750 European ancestry individuals, using adenosine diphosphate-induced platelet reactivity and major cardiovascular and cerebrovascular events as outcome parameters. GWAS for platelet reactivity revealed a strong signal for CYP2C19*2 (P value = 1.67e−33). After correction for CYP2C19*2 no other single-nucleotide polymorphism reached genomewide significance. GWAS for a combined clinical end point of cardiovascular death, myocardial infarction, or stroke (5.0% event rate), or a combined end point of cardiovascular death or myocardial infarction (4.7% event rate) showed no significant results, although in coronary artery disease, percutaneous coronary intervention, and acute coronary syndrome subgroups, mutations in SCOS5P1, CDC42BPA, and CTRAC1 showed genomewide significance (lowest P values: 1.07e−09, 4.53e−08, and 2.60e−10, respectively). CYP2C19*2 is the strongest genetic determinant of on-clopidogrel platelet reactivity. We identified three novel associations in clinical outcome subgroups, suggestive for each of these outcomes. © 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics."
}