ArticleBlood2014
Genetic variant in folate homeostasis is associated with lower warfarin dose in African Americans.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- An assessment of the impact of pharmacogenomics on health disparities: a systematic literature review.Pharmacogenomics · 2017Pooled it
- A Pharmacogenetic Prediction Model of Progression-Free Survival in Breast Cancer using Genome-Wide Genotyping Data from CALGB 40502 (Alliance).Clinical pharmacology and therapeutics · 2019Trial
- Targeted next-generation sequencing of genes involved in Warfarin Pharmacodynamics and pharmacokinetics pathways using the Saudi Warfarin Pharmacogenetic study (SWAP).The pharmacogenomics journal · 2023Article
- Article
- Warfarin Dosing in Patients With CYP2C9*5 Variant Alleles.Clinical pharmacology and therapeutics · 2022Article
- Translational Pharmacogenomics: Discovery, Evidence Synthesis and Delivery of Race-Conscious Medicine.Clinical pharmacology and therapeutics · 2021Review
- Genomewide Association Studies in Pharmacogenomics.Clinical pharmacology and therapeutics · 2021Review
- Pharmacogenomics in Cardiovascular Diseases.Current protocols · 2021Article
- Pharmacogenomics for Primary Care: An Overview.Genes · 2020Review
- Predicting venous thromboembolism risk from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges.Human mutation · 2019Article
- Identifying mutation-driven changes in gene functionality that lead to venous thromboembolism.Human mutation · 2019Article
- Pharmacogenomics in dermatology: tools for understanding gene-drug associations.Seminars in cutaneous medicine and surgery · 2019Review
- Identification of a Genomic Region betweenClinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Identifying core biological processes distinguishing human eye tissues with precise systems-level gene expression analyses and weighted correlation networks.Human molecular genetics · 2018Article
- VKORC1-1639A allele influences warfarin maintenance dosage among Blacks receiving warfarin anticoagulation: a retrospective cohort study.Future cardiology · 2018Article
- The Diversity of REcent and Ancient huMan (DREAM): A New Microarray for Genetic Anthropology and Genealogy, Forensics, and Personalized Medicine.Genome biology and evolution · 2017Article
- Population differences in S-warfarin pharmacokinetics among African Americans, Asians and whites: their influence on pharmacogenetic dosing algorithms.The pharmacogenomics journal · 2017Article
- Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans.Genome medicine · 2017Article
- Working toward precision medicine: Predicting phenotypes from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges.Human mutation · 2017Article
- Reports from CAGI: The Critical Assessment of Genome Interpretation.Human mutation · 2017Article
Corrections and comments
- Commented on by
Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
The anticoagulant warfarin has >30 million prescriptions per year in the United States. Doses can vary 20-fold between patients, and incorrect dosing can result in serious adverse events. Variation in warfarin pharmacokinetic and pharmacodynamic genes, such as CYP2C9 and VKORC1, do not fully explain the dose variability in African Americans. To identify additional genetic contributors to warfarin dose, we exome sequenced 103 African Americans on stable doses of warfarin at extremes (≤ 35 and ≥ 49 mg/week). We found an association between lower warfarin dose and a population-specific regulatory variant, rs7856096 (P = 1.82 × 10(-8), minor allele frequency = 20.4%), in the folate homeostasis gene folylpolyglutamate synthase (FPGS). We replicated this association in an independent cohort of 372 African American subjects whose stable warfarin doses represented the full dosing spectrum (P = .046). In a combined cohort, adding rs7856096 to the International Warfarin Pharmacogenetic Consortium pharmacogenetic dosing algorithm resulted in a 5.8 mg/week (P = 3.93 × 10(-5)) decrease in warfarin dose for each allele carried. The variant overlaps functional elements and was associated (P = .01) with FPGS gene expression in lymphoblastoid cell lines derived from combined HapMap African populations (N = 326). Our results provide the first evidence linking genetic variation in folate homeostasis to warfarin response.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.