Evidence map›Paper›PMID 27381900›Full record

ArticleHypertension (Dallas, Tex. : 1979)2016

A Genetic Response Score for Hydrochlorothiazide Use: Insights From Genomics and Metabolomics Integration.

Mohamed H Shahin, Yan Gong, Caitrin W McDonough, Daniel M Rotroff, Amber L Beitelshees, Timothy J Garrett, John G Gums, Alison Motsinger-Reif, Arlene B Chapman, Stephen T Turner and 6 more

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

Article in Hypertension (Dallas, Tex. : 1979), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

14 citing papers in PubMed, 27 citations in OpenAlex.

  1. Trial
  2. Article
  3. Application of omics in hypertension and resistant hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2022
    Review
  4. Plasma metabolomic profiles associated with hypertension and blood pressure in response to thiazide diuretics.Hypertension research : official journal of the Japanese Society of Hypertension · 2022
    Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. The Future of "Omics" in Hypertension.The Canadian journal of cardiology · 2017
    Review
  14. Metabolomics enables precision medicine: "A White Paper, Community Perspective".Metabolomics : Official journal of the Metabolomic Society
    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

16 authors at 5 institutions in 1 country.

Mohamed H ShahinFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Yan GongFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Caitrin W McDonoughFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Daniel M RotroffFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Amber L BeitelsheesFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Timothy J GarrettFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
John G GumsFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Alison Motsinger-ReifFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Arlene B ChapmanFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Stephen T TurnerFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Eric BoerwinkleFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Reginald F FryeFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Oliver FiehnFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Rhonda M Cooper-DeHoffFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Rima Kaddurah-DaoukFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.).
Julie A JohnsonFrom the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (M.H.S., Y.G., C.W.M., J.G.G., R.F.F., R.M.C.-D., J.A.J.) and Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine (T.J.G.), University of Florida, Gainesville; Department of Statistics, Bioinformatics Research Center, North Carolina State University, Raleigh (D.M.R., A.M.-R.); Department of Medicine, University of Maryland, Baltimore (A.L.B.); Department of Medicine, Emory University, Atlanta, GA (A.B.C.); Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN (S.T.T.); Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, (E.B.); Department of Molecular and Cellular Biology and Genome Center, University of California, Davis (O.F.); and Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC (R.K.-D.). johnson@cop.ufl.edu.
Emory University · USMayo Clinic · USThe University of Texas Health Science Center at Houston · USUniversity of Maryland, Baltimore · USNorth Carolina State University · US

Funding

Mayo Clinic Center for Translational Science ActivitiesUL1TR000135 · NCATS · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 2012 to 2015
$41.2M
Using social networks to map and evaluate team science across CTSA hubsUL1TR001427 · NCATS · UNIVERSITY OF FLORIDA · PI MITCHELL, DUANE A. · 2015 to 2024
$37.2M
Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8M
Pharmacogenomic Evaluation of Antihypertensive ResponsesU01GM074492 · NIGMS · UNIVERSITY OF FLORIDA · PI JOHNSON, JULIE A. · 2005 to 2014
$20.7M
UF Clinical and Translational Science AwardUL1TR000064 · NCATS · UNIVERSITY OF FLORIDA · PI NELSON, DAVID R · 2012 to 2014
$12.2M
West Coast Central Comprehensive Metabolomics Resource Core (WC3MRC)U24DK097154 · NIDDK · UNIVERSITY OF CALIFORNIA AT DAVIS · PI FIEHN, OLIVER · 2012 to 2017
$9.9M
Together: Transforming and Translating Discovery to Improve HealthKL2TR001429 · NCATS · UNIVERSITY OF FLORIDA · PI GUIRGIS, FAHEEM W, LEEUWENBURGH, CHRISTIAAN · 2015 to 2023
$5.5M
Metabolomics Network for Drug Response PhenotypeRC2GM092729 · NIGMS · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F · 2009 to 2010
$4.5M
American Heart Association-American Stroke Association 14PRE20460115NCATS NIH HHS KL2 TR001429NCATS NIH HHS UL1 TR000064NCATS NIH HHS UL1 TR000135NCATS NIH HHS UL1 TR000454NCATS NIH HHS UL1 TR001427NIDDK NIH HHS U24 DK097154NIGMS NIH HHS RC2 GM092729NIGMS NIH HHS U01 GM074492
6 · The paper itself

Abstract

Hydrochlorothiazide is among the most commonly prescribed antihypertensives; yet, <50% of hydrochlorothiazide-treated patients achieve blood pressure (BP) control. Herein, we integrated metabolomic and genomic profiles of hydrochlorothiazide-treated patients to identify novel genetic markers associated with hydrochlorothiazide BP response. The primary analysis included 228 white hypertensives treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. Genome-wide analysis was conducted using Illumina Omni 1 mol/L-Quad Chip, and untargeted metabolomics was performed on baseline fasting plasma samples using a gas chromatography-time-of-flight mass spectrometry platform. We found 13 metabolites significantly associated with hydrochlorothiazide systolic BP (SBP) and diastolic BP (DBP) responses (false discovery rate, <0.05). In addition, integrating genomic and metabolomic data revealed 3 polymorphisms (rs2727563 PRKAG2, rs12604940 DCC, and rs13262930 EPHX2) along with arachidonic acid, converging in the netrin signaling pathway (P=1×10(-5)), as potential markers, significantly influencing hydrochlorothiazide BP response. We successfully replicated the 3 genetic signals in 212 white hypertensives treated with hydrochlorothiazide and created a response score by summing their BP-lowering alleles. We found patients carrying 1 response allele had a significantly lower response than carriers of 6 alleles (∆SBP/∆DBP: -1.5/1.2 versus -16.3/-10.4 mm Hg, respectively, SBP score, P=1×10(-8) and DBP score, P=3×10(-9)). This score explained 11.3% and 11.9% of the variability in hydrochlorothiazide SBP and DBP responses, respectively, and was further validated in another independent study of 196 whites treated with hydrochlorothiazide (DBP score, P=0.03; SBP score, P=0.07). This study suggests that PRKAG2, DCC, and EPHX2 might be important determinants of hydrochlorothiazide BP response.

Indexed as

AdultAgedAMP-Activated Protein KinasesAntihypertensive AgentsBlood Pressure Monitoring, AmbulatoryCohort StudiesDCC ReceptorEpoxide HydrolasesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansHydrochlorothiazideHypertensionMaleMetabolomicsAMP-Activated Protein KinasesAntihypertensive AgentsDCC protein, humanDCC ReceptorEPHX2 protein, humanEpoxide HydrolasesHydrochlorothiazidePRKAG2 protein, humanReceptors, Cell SurfaceTumor Suppressor Proteinsgenome-wide association studyhydrochlorothiazidehypertensionmetabolomicspharmacogenetics

Identifiers

PMID27381900
PMCPMC4982802
OpenAlexW2467620689

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.