Evidence map›Paper›PMID 29737278›Full record

ArticleeLife2018

Determining the genetic basis of anthracycline-cardiotoxicity by molecular response QTL mapping in induced cardiomyocytes.

David A Knowles, Courtney K Burrows, John D Blischak, Kristen M Patterson, Daniel J Serie, Nadine Norton, Carole Ober, Jonathan K Pritchard, Yoav Gilad

Open access · goldAbstract read
In one paragraph

Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
16.0field-weighted citation impact, top 1% 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

73 citing papers in PubMed, 129 citations in OpenAlex.

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  8. Caught in the crossfire: cardiac complications of cancer therapy.The Journal of clinical investigation · 2026
    Review
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  17. Predicting oncology drug-induced cardiotoxicity with donor-specific iPSC-CMs-a proof-of-concept study with doxorubicin.Toxicological sciences : an official journal of the Society of Toxicology · 2024
    Article
  18. Article
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13 more citing papers are in PubMed but not listed here.

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 5 institutions in 1 country.

David A Knowles *Department of Genetics, Stanford University, Stanford, United States.ORCID http://orcid.org/0000-0002-7408-146X
Courtney K Burrows *Department of Human Genetics, University of Chicago, Chicago, United States.
John D BlischakDepartment of Human Genetics, University of Chicago, Chicago, United States.ORCID http://orcid.org/0000-0003-2634-9879
Kristen M PattersonDepartment of Human Genetics, University of Chicago, Chicago, United States.
Daniel J SerieDepartment of Health Sciences Research, Mayo Clinic, Jacksonville, United States.
Nadine NortonDepartment of Cancer Biology, Mayo Clinic, Jacksonville, United States.
Carole OberDepartment of Human Genetics, University of Chicago, Chicago, United States.
Jonathan K PritchardDepartment of Genetics, Stanford University, Stanford, United States.ORCID https://orcid.org/0000-0002-8828-5236
Yoav GiladDepartment of Human Genetics, University of Chicago, Chicago, United States.ORCID https://orcid.org/0000-0001-8284-8926
University of Chicago · USHoward Hughes Medical Institute · USMayo Clinic in Florida · USStanford University · USWinnMed · US

Funding

Integration of genetic association mapping and functional data to elucidate genetic mechanisms of diseaseR01HG008140 · NHGRI · STANFORD UNIVERSITY · PI JONATHAN K PRITCHARD · 2016 to 2026
$7.3M
Integrating genomics and gene expression analyses to map CVD-associated lociR01HL092206 · NHLBI · UNIVERSITY OF CHICAGO · PI GILAD, YOAV · 2009 to 2021
$7.3M
Decoding the regulatory architecture of the human genome across cell types, individuals and diseaseU01HG009431 · NHGRI · STANFORD UNIVERSITY · PI PRITCHARD, JONATHAN K · 2017 to 2021
$3.5M
Howard Hughes Medical InstituteNHGRI NIH HHS HG008140NHGRI NIH HHS HG009431NHGRI NIH HHS R01 HG008140NHGRI NIH HHS U01 HG009431NHLBI NIH HHS HL092206NHLBI NIH HHS R01 HL092206NIH HHS TL1 TR 432-7
6 · The paper itself

Abstract

Anthracycline-induced cardiotoxicity (ACT) is a key limiting factor in setting optimal chemotherapy regimes, with almost half of patients expected to develop congestive heart failure given high doses. However, the genetic basis of sensitivity to anthracyclines remains unclear. We created a panel of iPSC-derived cardiomyocytes from 45 individuals and performed RNA-seq after 24 hr exposure to varying doxorubicin dosages. The transcriptomic response is substantial: the majority of genes are differentially expressed and over 6000 genes show evidence of differential splicing, the later driven by reduced splicing fidelity in the presence of doxorubicin. We show that inter-individual variation in transcriptional response is predictive of in vitro cell damage, which in turn is associated with in vivo ACT risk. We detect 447 response-expression quantitative trait loci (QTLs) and 42 response-splicing QTLs, which are enriched in lower ACT GWAS [Formula: see text]-values, supporting the in vivo relevance of our map of genetic regulation of cellular response to anthracyclines.

Indexed as

CardiotoxicityAnthracyclinesCells, CulturedDoxorubicinGene Expression ProfilingGenome-Wide Association StudyHumansMyocytes, CardiacQuantitative Trait LociSequence Analysis, RNAAnthracyclinesDoxorubicinanthracycline-induced toxicityDoxorubicinevolutionary biologygeneticsgenomicshumanhuman biologyiPSC-derived differentiated cellsmedicineoxidative damageresponse expression QTL

Identifiers

PMID29737278
PMCPMC6010343
OpenAlexW2951535811

What OpenQuestion holds

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LicenceCC BY
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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.