ArticlePloS one2013
Genome wide analysis of drug-induced torsades de pointes: lack of common variants with large effect sizes.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Pharmacogenomic markers associated with drug-induced QT prolongation: a systematic review.PharmacogenomicsPooled it
- Functional Profiling ofCirculation. Genomic and precision medicine · 2025Article
- Genetic risk factors for drug-induced long QT syndrome: findings from a large real-world case-control study.Pharmacogenomics · 2024Observational
- Human Genetics of Cardiac Arrhythmias.Advances in experimental medicine and biology · 2024Review
- Heart rhythmFrontiers in cardiovascular medicine · 2024Article
- Variants TaggingGenes · 2022Article
- The genetics of drug-induced QT prolongation: evaluating the evidence for pharmacodynamic variants.Pharmacogenomics · 2022Review
- The role of pharmacogenomics in contemporary cardiovascular therapy: a position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.European heart journal. Cardiovascular pharmacotherapy · 2022Article
- Genetics and genomics of arrhythmic risk: current and future strategies to prevent sudden cardiac death.Nature reviews. Cardiology · 2021Review
- The Interface of Therapeutics and Genomics in Cardiovascular Medicine.Cardiovascular drugs and therapy · 2021Review
- Real-time clinical note monitoring to detect conditions for rapid follow-up: A case study of clinical trial enrollment in drug-induced torsades de pointes and Stevens-Johnson syndrome.Journal of the American Medical Informatics Association : JAMIA · 2021Article
- Genome-wide association studies of cardiac electrical phenotypes.Cardiovascular research · 2020Review
- Pharmacogenomics.Lancet (London, England) · 2019Review
- A current understanding of drug-induced QT prolongation and its implications for anticancer therapy.Cardiovascular research · 2019Review
- Whole genome sequencing to identify predictive markers for the risk of drug-induced interstitial lung disease.PloS one · 2019Article
- Using iPSC Models to Probe Regulation of Cardiac Ion Channel Function.Current cardiology reports · 2018Review
- Opportunities and Challenges in Cardiovascular Pharmacogenomics: From Discovery to Implementation.Circulation research · 2018Review
- Drugs and life-threatening ventricular arrhythmia risk: results from the DARE study cohort.BMJ open · 2017Article
- Common Genetic Variant Risk Score Is Associated With Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study.Circulation · 2017Article
- Recapitulation of Clinical Individual Susceptibility to Drug-Induced QT Prolongation in Healthy Subjects Using iPSC-Derived Cardiomyocytes.Stem cell reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 16 institutions in 6 countries.
Funding
Abstract
Marked prolongation of the QT interval on the electrocardiogram associated with the polymorphic ventricular tachycardia Torsades de Pointes is a serious adverse event during treatment with antiarrhythmic drugs and other culprit medications, and is a common cause for drug relabeling and withdrawal. Although clinical risk factors have been identified, the syndrome remains unpredictable in an individual patient. Here we used genome-wide association analysis to search for common predisposing genetic variants. Cases of drug-induced Torsades de Pointes (diTdP), treatment tolerant controls, and general population controls were ascertained across multiple sites using common definitions, and genotyped on the Illumina 610k or 1M-Duo BeadChips. Principal Components Analysis was used to select 216 Northwestern European diTdP cases and 771 ancestry-matched controls, including treatment-tolerant and general population subjects. With these sample sizes, there is 80% power to detect a variant at genome-wide significance with minor allele frequency of 10% and conferring an odds ratio of ≥2.7. Tests of association were carried out for each single nucleotide polymorphism (SNP) by logistic regression adjusting for gender and population structure. No SNP reached genome wide-significance; the variant with the lowest P value was rs2276314, a non-synonymous coding variant in C18orf21 (p = 3×10(-7), odds ratio = 2, 95% confidence intervals: 1.5-2.6). The haplotype formed by rs2276314 and a second SNP, rs767531, was significantly more frequent in controls than cases (p = 3×10(-9)). Expanding the number of controls and a gene-based analysis did not yield significant associations. This study argues that common genomic variants do not contribute importantly to risk for drug-induced Torsades de Pointes across multiple drugs.
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Registered trials
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.