Evidence map›Paper›PMID 28135054›Full record

ArticleJournal of thrombosis and haemostasis : JTH2017

Integrated analysis of genetic variation and gene expression reveals novel variant for increased warfarin dose requirement in African Americans.

W Hernandez, E R Gamazon, K Aquino-Michaels, E Smithberger, T J O'Brien, A F Harralson, M Tuck, A Barbour, L H Cavallari, M A Perera

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Warfarin Dosing in Patients With CYP2C9*5 Variant Alleles.Clinical pharmacology and therapeutics · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 2 countries.

W HernandezSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
E R GamazonDivision of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
K Aquino-MichaelsSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
E SmithbergerSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
T J O'BrienDepartment of Pharmacology and Physiology, George Washington University, Washington, DC, USA.
A F HarralsonDepartment of Medicine, George Washington University, Washington, DC, USA.
M TuckVeterans Affairs Medical Center, Washington, DC, USA.
A BarbourDepartment of Medicine, George Washington University, Washington, DC, USA.
L H CavallariDepartment of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
M A PereraDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
George Washington University · USUniversity of Chicago · USAcademic Medical Center · NLNorthwestern University · USUniversity of Florida · USVeterans Health Administration · US

Funding

MULTIDISCIPLINARY CARDIAC SCIENCEST32HL007381 · NHLBI · UNIVERSITY OF CHICAGO · PI JEANNE M DECARA, Yoav Gilad · 1985 to 2026
$12.5M
Harnessing GTEx to Create Transcriptome Knowledge and Inform Disease BiologyR01MH101820 · NIMH · UNIVERSITY OF CHICAGO · PI COX, NANCY J, NICOLAE, DAN LIVIU · 2013 to 2015
$2.3M
Health disparity in pharmacogenomics: African American SNPs and drug metabolismR01MD009217 · NIMHD · UNIVERSITY OF CHICAGO · PI PERERA, MINOLI A · 2014 to 2018
$2.0M
Using the Transcriptome for SNP and Gene AnnotationR01MH090937 · NIMH · UNIVERSITY OF CHICAGO · PI COX, NANCY J, NICOLAE, DAN LIVIU · 2010 to 2012
$825k
The implementation of a pharmacogenomics-based algorithm for warfarin dosingK23HL089808 · NHLBI · UNIVERSITY OF CHICAGO · PI PERERA, MINOLI A · 2009 to 2013
$601k
Comprehensive studies of novel SNPs affecting warfarin dose in African AmericansR21HL106097 · NHLBI · UNIVERSITY OF CHICAGO · PI PERERA, MINOLI A · 2011 to 2012
$437k
NHLBI NIH HHS K23 HL089808NHLBI NIH HHS R21 HL106097NHLBI NIH HHS T32 HL007381NIMHD NIH HHS R01 MD009217NIMH NIH HHS R01 MH090937NIMH NIH HHS R01 MH101820
6 · The paper itself

Abstract

Essentials Genetic variants controlling gene regulation have not been explored in pharmacogenomics. We tested liver expression quantitative trait loci for association with warfarin dose response. A novel predictor for increased warfarin dose response in African Americans was identified. Precision medicine must take into account population-specific variation in gene regulation. SUMMARY: Background Warfarin is commonly used to control and prevent thromboembolic disorders. However, because of warfarin's complex dose-requirement relationship, safe and effective use is challenging. Pharmacogenomics-guided warfarin dosing algorithms that include the well-established VKORC1 and CYP2C9 polymorphisms explain only a small proportion of inter-individual variability in African Americans (AAs). Objectives We aimed to assess whether transcriptomic analyses could be used to identify regulatory variants associated with warfarin dose response in AAs. Patients/Methods We identified a total of 56 expression quantitative trait loci (eQTLs) for CYP2C9, VKORC1 and CALU derived from human livers and evaluated their association with warfarin dose response in two independent AA warfarin patient cohorts. Results We found that rs4889606, a strong cis-eQTL for VKORC1 (log

Indexed as

Genetic VariationAdultAgedAlgorithmsBlack or African AmericanCalcium-Binding ProteinsCohort StudiesCytochrome P-450 CYP2C9FemaleGene Expression ProfilingGene Expression RegulationGenotypeHumansLinkage DisequilibriumLiverMaleCalcium-Binding ProteinsCALU protein, humanCYP2C9 protein, humanCytochrome P-450 CYP2C9Vitamin K Epoxide ReductasesVKORC1 protein, humanWarfarinAfrican Americanpharmacogeneticsquantitative trait locithromboembolismwarfarin

Identifiers

PMID28135054
PMCPMC5862636
OpenAlexW2581368802

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.