Evidence map›Paper›PMID 23459443›Full record

SynthesisThe pharmacogenomics journal2014

Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval.

C L Avery, C M Sitlani, D E Arking, D K Arnett, J C Bis, E Boerwinkle, B M Buckley, Y-D Ida Chen, A J M de Craen, M Eijgelsheim and 44 more

Open access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The pharmacogenomics journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 5 pooled it
3.0field-weighted citation impact, top 9% 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

23 citing papers in PubMed, 5 syntheses or guidelines pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Article
  7. Observational
  8. Precision Medicine in Antidepressants Treatment.Handbook of experimental pharmacology · 2023
    Review
  9. Review
  10. Review
  11. Genetic and Molecular Aspects of Drug-Induced QT Interval Prolongation.International journal of molecular sciences · 2021
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. 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

54 authors at 20 institutions in 5 countries.

C L AveryDepartment of Epidemiology, Bank of America Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
C M SitlaniCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
D E ArkingMcKusick-Nathans Institute of Genetic Medicine and Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
D K ArnettDepartment of Epidemiology, The University of Alabama at Birmingham, Birmingham, AL, USA.
J C BisCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
E BoerwinkleDivision of Epidemiology and Center for Human Genetics, The University of Texas Health Science Center, Houston, TX, USA.
B M BuckleyDepartment of Pharmacology and Therapeutics, University College Cork, Cork, UK.
Y-D Ida ChenCedars-Sinai Medical Center, Los Angeles, CA, USA.
A J M de CraenDepartment of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
M EijgelsheimDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
D EnquobahrieCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
D S EvansCalifornia Pacific Medical Center Research Institute, San Francisco, CA, USA.
I FordRobertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
M E GarciaLaboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD, USA.
V GudnasonIcelandic Heart Association, Kopavogur, Iceland.
T B HarrisLaboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD, USA.
S R Heckbert1] Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA [2] Department of Epidemiology, University of Washington, Seattle, WA, USA.
H HochnerCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
A Hofman1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands.
W-C HsuehDepartment of Medicine, University of California, San Francisco, CA, USA.
A Isaacs1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Centre for Medical Systems Biology, Leiden, The Netherlands.
J W JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
P KnektTHL-National Institute for Health and Welfare, Helsinki, Finland.
J A Kors1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands [2] Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands.
B P Krijthe1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands.
K KristianssonTHL-National Institute for Health and Welfare, Helsinki, Finland.
M LaaksonenTHL-National Institute for Health and Welfare, Helsinki, Finland.
Y LiuDepartment of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University, Winston-Salem, NC, USA.
X LiCedars-Sinai Medical Center, Los Angeles, CA, USA.
P W MacfarlaneInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
C Newton-Cheh1] Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA [2] Center for Human Genetic Research, Cardiovascular Research Center, Harvard Medical School, Boston, MA, USA [3] Massachusetts General Hospital, Boston, MA, USA.
M S NieminenDivision of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
B A Oostra1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Centre for Medical Systems Biology, Leiden, The Netherlands.
G M Peloso1] National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA [2] Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
K PorthanDivision of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
K RiceDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
F F Rivadeneira1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands [3] Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
J I RotterCedars-Sinai Medical Center, Los Angeles, CA, USA.
V SalomaaTHL-National Institute for Health and Welfare, Helsinki, Finland.
N SattarBHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, UK.
D S Siscovick1] Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA [2] Department of Epidemiology, University of Washington, Seattle, WA, USA.
P E SlagboomDepartment of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
A V SmithIcelandic Heart Association, Kopavogur, Iceland.
N SotoodehniaDivision of Cardiology, University of Washington, Seattle, WA, USA.
D J StottAcademic Section of Geriatric Medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
B H Stricker1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands [3] Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands [4] Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
T StürmerDepartment of Epidemiology, Bank of America Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
S TrompetDepartment of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
A G Uitterlinden1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands [3] Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
C van Duijn1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Centre for Medical Systems Biology, Leiden, The Netherlands.
R G J WestendorpDepartment of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
J C Witteman1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands.
E A Whitsel1] Department of Epidemiology, Bank of America Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Departments of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
B M Psaty1] Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA [2] Department of Epidemiology, University of Washington, Seattle, WA, USA [3] Departments of Medicine, University of Washington, Seattle, WA, USA [4] Department of Health Services, University of Washington, Seattle, WA, USA [5] Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
University of Washington · USErasmus MC · NLLeiden University Medical Center · NLFinnish Institute for Health and Welfare · FINetherlands Consortium for Healthy Ageing · NLCedars-Sinai Medical Center · USUniversity of Glasgow · GBBank of America · USHelsinki University Hospital · FIIcelandic Heart Association · ISNational Institute on Aging · USCalifornia Pacific Medical Center · USCenter for Human Genetics · USCentre for Medical Systems Biology · NLJohns Hopkins University · USMassachusetts Institute of Technology · USNational Heart Lung and Blood Institute · USUniversity of Alabama at Birmingham · USUniversity of California, San Francisco · USUniversity of North Carolina at Chapel Hill · US

Funding

Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
ZONA-FREE HAMSTER OVA ASSAY AS AN INDICATOR OF MALE FERTILITYM01RR000425 · NCRR · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI ANDERSON, GAIL V · 1985 to 2011
$74.2M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024156 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2006 to 2011
$53.0M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
Genome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2M
MULTIDISCIPLINARY RESEARCH TRAINING IN CARDIOLOGYT32HL007208 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Patrick Thomas Ellinor, David E Sosnovik · 1985 to 2026
$16.1M
UCLA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR033176 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2011 to 2011
$15.5M
Epidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8M
Multi-Ethnic Study of Atherosclerosis (MESA) StudyR01HL071205 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI ROTTER, JEROME I · 2003 to 2007
$10.4M
Exceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
NCATS NIH HHS UL1 TR000124NCRR NIH HHS M01 RR000425NCRR NIH HHS UL1 RR024156NCRR NIH HHS UL1 RR025005NCRR NIH HHS UL1RR025005NCRR NIH HHS UL1 RR033176NCRR NIH HHS UL 1RR033176NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01 HG004402NHGRI NIH HHS U01HG004402NHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HL075366NHLBI NIH HHS HL080025NHLBI NIH HHS HL080295NHLBI NIH HHS HL087652NHLBI NIH HHS HL105756NHLBI NIH HHS K23 HL080025NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC045133NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC075150NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N02 HL064275NHLBI NIH HHS N02 HL064278NHLBI NIH HHS R00 HL098458NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL071205NHLBI NIH HHS R01 HL075366NHLBI NIH HHS R01 HL080295NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01HL087641NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL088457NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01HL59367NHLBI NIH HHS T32 HL007208NHLBI NIH HHS U01 HL080295NIA NIH HHS 1R01AG032098-01A1NIA NIH HHS AG-023629NIA NIH HHS AG-027058NIA NIH HHS AG-20098NIA NIH HHS N01 AG062101NIA NIH HHS N01 AG062103NIA NIH HHS N01 AG062106NIA NIH HHS R01 AG015928NIA NIH HHS R01 AG020098NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG027058NIA NIH HHS R01 AG032098NIA NIH HHS R56 AG020098NIA NIH HHS R56 AG023629NIDDK NIH HHS DK063491NIDDK NIH HHS P30 DK063491
6 · The paper itself

Abstract

Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the 'missing heritability' of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/tetracyclic antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug-gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug-single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null (Pinteraction>5.0 × 10(-8)). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.

Indexed as

Gene-Environment InteractionPharmacogeneticsQuantitative Trait, HeritableComputer SimulationCross-Sectional StudiesDrug-Related Side Effects and Adverse ReactionsElectrocardiographyGenome-Wide Association StudyHumansLinear ModelsLong QT SyndromeMarkov ChainsPolymorphism, Single NucleotideWhite People

Identifiers

PMID23459443
PMCPMC3766418
OpenAlexW2123597934

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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.