Evidence map›Paper›PMID 28099408›Full record

Trial reportPharmacogenetics and genomics2017

Multiphenotype association study of patients randomized to initiate antiretroviral regimens in AIDS Clinical Trials Group protocol A5202.

Anurag Verma, Yuki Bradford, Shefali S Verma, Sarah A Pendergrass, Eric S Daar, Charles Venuto, Gene D Morse, Marylyn D Ritchie, David W Haas

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Pharmacogenetics and genomics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-weighted citation impact, top 22% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Influence of tissue context on gene prioritization for predicted transcriptome-wide association studies.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2019
    Trial
  2. Article
  3. Article
  4. Article
  5. Review
  6. PRECISION MEDICINE: FROM DIPLOTYPES TO DISPARITIES TOWARDS IMPROVED HEALTH AND THERAPIES.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2018
    Article
  7. Evaluation of PrediXcan for prioritizing GWAS associations and predicting gene expression.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2018
    Article
  8. 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

9 authors at 2 institutions in 1 country.

Anurag VermaaThe Center for Systems Genomics, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park bBiomedical and Translational Informatics, Geisinger Health System, Danville, Pennsylvania cLos Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, California dUniversity of Rochester Medical Center, Rochester eDepartment of Pharmacy Practice, Center for Integrated Global Biomedical Sciences, University at Buffalo, SUNY, Buffalo, New York fVanderbilt University School of Medicine gMeharry Medical College, Nashville, Tennessee, USA.
Yuki Bradford
Shefali S Verma
Sarah A Pendergrass
Eric S Daar
Charles Venuto
Gene D Morse
Marylyn D Ritchie
David W Haas
Creative Commons · USPennsylvania State University · US

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
WOMEN'S HEALTH AGENDAU01AI038858 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI BENSON, CONSTANCE ANN · 1996 to 2008
$157.5M
AIDS Clinical Trials Group NetworkU01AI068636 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI KURITZKES, DANIEL R. · 2006 to 2010
$147.1M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6M
STATISTICAL AND DATA MANAGEMENT CENTERU01AI038855 · NIAID · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI HUGHES, MICHAEL DAVID · 1996 to 2006
$78.1M
Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Ann M Chahroudi, Colleen F Kelley · 2002 to 2026
$74.0M
Statistical and Data Management Center for the AIDS Clinical Trials GroupU01AI068634 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HUGHES, MICHAEL DAVID · 2006 to 2010
$71.9M
University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit 2024 SupplementUM1AI069423 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, MINA CHRISTINE HOSSEINIPOUR · 2012 to 2026
$71.8M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024156 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2006 to 2011
$53.0M
NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR001417NCRR NIH HHS KL2 RR025776NCRR NIH HHS M01 RR000046NCRR NIH HHS M01 RR000051NCRR NIH HHS UL1 RR024156NCRR NIH HHS UL1 RR024160NCRR NIH HHS UL1 RR024996NCRR NIH HHS UL1 RR025747NCRR NIH HHS UL1 RR025777NIAID NIH HHS K23 AI108355NIAID NIH HHS P30 AI045008NIAID NIH HHS P30 AI050409NIAID NIH HHS P30 AI050410NIAID NIH HHS P30 AI054907NIAID NIH HHS P30 AI054999NIAID NIH HHS P30 AI073961NIAID NIH HHS P30 AI110527NIAID NIH HHS R01 AI058740NIAID NIH HHS R01 AI077505NIAID NIH HHS U01 AI025859NIAID NIH HHS U01 AI027658NIAID NIH HHS U01 AI027661NIAID NIH HHS U01 AI027666NIAID NIH HHS U01 AI027675NIAID NIH HHS U01 AI032782NIAID NIH HHS U01 AI034853NIAID NIH HHS U01 AI038855NIAID NIH HHS U01 AI038858NIAID NIH HHS U01 AI046339NIAID NIH HHS U01 AI046370NIAID NIH HHS U01 AI046376NIAID NIH HHS U01 AI068634NIAID NIH HHS U01 AI068636NIAID NIH HHS U01 AI069415NIAID NIH HHS U01 AI069418NIAID NIH HHS U01 AI069419NIAID NIH HHS U01 AI069423NIAID NIH HHS U01 AI069424NIAID NIH HHS U01 AI069428NIAID NIH HHS U01 AI069432NIAID NIH HHS U01 AI069434NIAID NIH HHS U01 AI069439NIAID NIH HHS U01 AI069447NIAID NIH HHS U01 AI069450NIAID NIH HHS U01 AI069452NIAID NIH HHS U01 AI069465NIAID NIH HHS U01 AI069467NIAID NIH HHS U01 AI069470NIAID NIH HHS U01 AI069471NIAID NIH HHS U01 AI069472NIAID NIH HHS U01 AI069474NIAID NIH HHS U01 AI069477NIAID NIH HHS U01 AI069484NIAID NIH HHS U01 AI069494NIAID NIH HHS U01 AI069495NIAID NIH HHS U01 AI069501NIAID NIH HHS U01 AI069502NIAID NIH HHS U01 AI069511NIAID NIH HHS U01 AI069513NIAID NIH HHS U01 AI069532NIAID NIH HHS U01 AI069556NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069415NIAID NIH HHS UM1 AI069418NIAID NIH HHS UM1 AI069419NIAID NIH HHS UM1 AI069423NIAID NIH HHS UM1 AI069424NIAID NIH HHS UM1 AI069428NIAID NIH HHS UM1 AI069432NIAID NIH HHS UM1 AI069434NIAID NIH HHS UM1 AI069439NIAID NIH HHS UM1 AI069447NIAID NIH HHS UM1 AI069450NIAID NIH HHS UM1 AI069452NIAID NIH HHS UM1 AI069465NIAID NIH HHS UM1 AI069467NIAID NIH HHS UM1 AI069470NIAID NIH HHS UM1 AI069471NIAID NIH HHS UM1 AI069472NIAID NIH HHS UM1 AI069474NIAID NIH HHS UM1 AI069477NIAID NIH HHS UM1 AI069484NIAID NIH HHS UM1 AI069494NIAID NIH HHS UM1 AI069495NIAID NIH HHS UM1 AI069496NIAID NIH HHS UM1 AI069501NIAID NIH HHS UM1 AI069502NIAID NIH HHS UM1 AI069511NIAID NIH HHS UM1 AI069513NIAID NIH HHS UM1 AI069532NIAID NIH HHS UM1 AI069556NIAID NIH HHS UM1 AI106701
6 · The paper itself

Abstract

backgroundHigh-throughput approaches are increasingly being used to identify genetic associations across multiple phenotypes simultaneously. Here, we describe a pilot analysis that considered multiple on-treatment laboratory phenotypes from antiretroviral therapy-naive patients who were randomized to initiate antiretroviral regimens in a prospective clinical trial, AIDS Clinical Trials Group protocol A5202. PARTICIPANTS AND

methodsFrom among 5 9545 294 polymorphisms imputed genome-wide, we analyzed 2544, including 2124 annotated in the PharmGKB, and 420 previously associated with traits in the GWAS Catalog. We derived 774 phenotypes on the basis of context from six variables: plasma atazanavir (ATV) pharmacokinetics, plasma efavirenz (EFV) pharmacokinetics, change in the CD4+ T-cell count, HIV-1 RNA suppression, fasting low-density lipoprotein-cholesterol, and fasting triglycerides. Permutation testing assessed the likelihood of associations being by chance alone. Pleiotropy was assessed for polymorphisms with the lowest P-values.

resultsThis analysis included 1181 patients. At P less than 1.5×10, most associations were not by chance alone. Polymorphisms with the lowest P-values for EFV pharmacokinetics (CYPB26 rs3745274), low-density lipoprotein -cholesterol (APOE rs7412), and triglyceride (APOA5 rs651821) phenotypes had been associated previously with those traits in previous studies. The association between triglycerides and rs651821 was present with ATV-containing regimens, but not with EFV-containing regimens. Polymorphisms with the lowest P-values for ATV pharmacokinetics, CD4 T-cell count, and HIV-1 RNA phenotypes had not been reported previously to be associated with that trait.

conclusionUsing data from a prospective HIV clinical trial, we identified expected genetic associations, potentially novel associations, and at least one context-dependent association. This study supports high-throughput strategies that simultaneously explore multiple phenotypes from clinical trials' datasets for genetic associations.

Indexed as

Polymorphism, Single NucleotideAcquired Immunodeficiency SyndromeAdultAnti-Retroviral AgentsApolipoprotein A-VApolipoproteins ECD4-Positive T-LymphocytesCytochrome P-450 CYP2B6FemaleHumansLymphocyte CountMaleMiddle AgedPharmacogenomic VariantsPhenotypePilot ProjectsAnti-Retroviral AgentsAPOA5 protein, humanApoE protein, humanApolipoprotein A-VApolipoproteins ECYP2B6 protein, humanCytochrome P-450 CYP2B6

Identifiers

PMID28099408
PMCPMC5285297
OpenAlexW2570376902

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.