ArticlePharmacogenetics and genomics2017
Genome-wide association and pathway analysis of left ventricular function after anthracycline exposure in adults.
Article 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 43 papers.
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Who cites it
43 citing papers in PubMed, 62 citations in OpenAlex.
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- Physiologically Relevant 3D CRISPR Screening Enhances Mechanistic Insight into Chemical Toxicity Compared to 2D Screening.bioRxiv : the preprint server for biology · 2025Article
- Meta-analysis of genome-wide association studies of doxorubicin-induced arrhythmia identifiesmedRxiv : the preprint server for health sciences · 2025Article
- Cancer, genetic susceptibility and risk of coronary artery disease: A prospective study.American journal of preventive cardiology · 2025Article
- Variants in structural cardiac genes in patients with cancer therapy-related cardiac dysfunction after anthracycline chemotherapy: a case control study.Cardio-oncology (London, England) · 2024Article
- Cardiovascular Biomarkers in Cardio-Oncology: Antineoplastic Drug Cardiotoxicity and Beyond.Biomolecules · 2024Review
- Functional Validation of Doxorubicin-Induced Cardiotoxicity-Related Genes.JACC. CardioOncology · 2024Article
- Anthracycline Toxicity: Light at the End of the Tunnel?Annual review of pharmacology and toxicology · 2024Review
- Racial Disparity in Anthracycline-induced Cardiotoxicity in Breast Cancer Patients.Biomedicines · 2023Review
- The Roles of Histone Lysine Methyltransferases in Heart Development and Disease.Journal of cardiovascular development and disease · 2023Review
- Pharmacogenomics and health disparities, are we helping?Frontiers in genetics · 2023Review
- Integrative network analysis interweaves the missing links in cardiomyopathy diseasome.Scientific reports · 2022Article
- New Biomarkers and Their Potential Role in Heart Failure Treatment Optimisation-An African Perspective.Journal of cardiovascular development and disease · 2022Review
- Exploration of the amino acid metabolic signature in anthracycline-induced cardiotoxicity using an optimized targeted metabolomics approach based on UPLC-MS/MS.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- A Novel Locus on 6p21.2 for Cancer Treatment-Induced Cardiac Dysfunction Among Childhood Cancer Survivors.Journal of the National Cancer Institute · 2022Article
- Novel molecular biomarkers of cancer therapy-induced cardiotoxicity in adult population: a scoping review.ESC heart failure · 2022Article
- Article
- Inter-Individual Variation and Cardioprotection in Anthracycline-Induced Heart Failure.Journal of clinical medicine · 2021Review
- Left Ventricular Systolic Function Has Strong Independent Genetic Background from Diastolic Function: A Classical Twin Study.Medicina (Kaunas, Lithuania) · 2021Article
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAnthracyclines are important chemotherapeutic agents, but their use is limited by cardiotoxicity. Candidate gene and genome-wide studies have identified putative risk loci for overt cardiotoxicity and heart failure, but there has been no comprehensive assessment of genomic variation influencing the intermediate phenotype of anthracycline-related changes in left ventricular (LV) function. The purpose of this study was to identify genetic factors influencing changes in LV function after anthracycline chemotherapy.
methodsWe conducted a genome-wide association study (GWAS) of change in LV function after anthracycline exposure in 385 patients identified from BioVU, a resource linking DNA samples to de-identified electronic medical record data. Variants with P values less than 1×10 were independently tested for replication in a cohort of 181 anthracycline-exposed patients from a prospective clinical trial. Pathway analysis was performed to assess combined effects of multiple genetic variants.
resultsBoth cohorts were middle-aged adults of predominantly European descent. Among 11 candidate loci identified in discovery GWAS, one single nucleotide polymorphism near PR domain containing 2, with ZNF domain (PRDM2), rs7542939, had a combined P value of 6.5×10 in meta-analysis. Eighteen Kyoto Encyclopedia of Gene and Genomes pathways showed strong enrichment for variants associated with the primary outcome. Identified pathways related to DNA repair, cellular metabolism, and cardiac remodeling.
conclusionUsing genome-wide association we identified a novel candidate susceptibility locus near PRDM2. Variation in genes belonging to pathways related to DNA repair, metabolism, and cardiac remodeling may influence changes in LV function after anthracycline exposure.
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