ArticleLancet (London, England)2013
Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study.
Article in Lancet (London, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 6 of them syntheses that pooled it.
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Who cites it
137 citing papers in PubMed, 6 syntheses or guidelines pooled it, 274 citations in OpenAlex.
- Meta-analysis of genome-wide association studies of stable warfarin dose in patients of African ancestry.Blood advances · 2024Pooled it
- Genomewide association analysis of warfarin dose requirements in Middle Eastern and North African populations.Clinical and translational science · 2022Pooled it
- Recommendations for Clinical Warfarin Genotyping Allele Selection: A Report of the Association for Molecular Pathology and the College of American Pathologists.The Journal of molecular diagnostics : JMD · 2020Guideline
- Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis.Clinical pharmacology and therapeutics · 2020Pooled it
- An assessment of the impact of pharmacogenomics on health disparities: a systematic literature review.Pharmacogenomics · 2017Pooled it
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update.Clinical pharmacology and therapeutics · 2017Guideline
- Genotype-Guided Dosing of Warfarin in Chinese Adults: A Multicenter Randomized Clinical Trial.Circulation. Genomic and precision medicine · 2020Trial
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- Pulmonary Embolism and ABO Blood Type: A Systematic Review.Diagnostics (Basel, Switzerland) · 2025Review
- Local ancestry-informed GWAS of warfarin dose requirement in African Americans identifies a CYP2C19 splicing QTL.American journal of human genetics · 2025Article
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- Being precise with anticoagulation to reduce adverse drug reactions: are we there yet?The pharmacogenomics journal · 2024Review
- Turkish Real Life Atrial Fibrillation in Clinical Practice: TRAFFIC Study.Anatolian journal of cardiology · 2024Article
- LA-GEM: imputation of gene expression with incorporation of Local Ancestry.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2024Article
- Pharmacogenomic knowledge and awareness among diverse patients treated with angiotensin converting enzyme inhibitors.Pharmacogenomics · 2023Article
- Population Pharmacogenomics in Croatia: Evaluating the PGx Allele Frequency and the Impact of Treatment Efficiency.International journal of molecular sciences · 2023Article
- Novel Gene Polymorphisms for Stable Warfarin Dose in a Korean Population: Genome-Wide Association Study.Biomedicines · 2023Article
77 more citing papers are in PubMed but not listed here.
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Authors and funding
42 authors at 18 institutions in 5 countries.
Funding
Abstract
backgroundVKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans.
methodsWe did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged ≥18 years) who were taking a stable maintenance dose of warfarin were obtained at International Warfarin Pharmacogenetics Consortium (IWPC) sites and the University of Alabama at Birmingham (Birmingham, AL, USA). Patients enrolled at IWPC sites but who were not used for discovery made up the independent replication cohort. All participants were genotyped. We did a stepwise conditional analysis, conditioning first for VKORC1 -1639G→A, followed by the composite genotype of CYP2C9*2 and CYP2C9*3. We prespecified a genome-wide significance threshold of p<5×10(-8) in the discovery cohort and p<0·0038 in the replication cohort.
findingsThe discovery cohort contained 533 participants and the replication cohort 432 participants. After the prespecified conditioning in the discovery cohort, we identified an association between a novel single nucleotide polymorphism in the CYP2C cluster on chromosome 10 (rs12777823) and warfarin dose requirement that reached genome-wide significance (p=1·51×10(-8)). This association was confirmed in the replication cohort (p=5·04×10(-5)); analysis of the two cohorts together produced a p value of 4·5×10(-12). Individuals heterozygous for the rs12777823 A allele need a dose reduction of 6·92 mg/week and those homozygous 9·34 mg/week. Regression analysis showed that the inclusion of rs12777823 significantly improves warfarin dose variability explained by the IWPC dosing algorithm (21% relative improvement).
interpretationA novel CYP2C single nucleotide polymorphism exerts a clinically relevant effect on warfarin dose in African Americans, independent of CYP2C9*2 and CYP2C9*3. Incorporation of this variant into pharmacogenetic dosing algorithms could improve warfarin dose prediction in this population.
fundingNational Institutes of Health, American Heart Association, Howard Hughes Medical Institute, Wisconsin Network for Health Research, and the Wellcome Trust.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.