ArticlemedRxiv : the preprint server for health sciences2025
Meta-analysis of genome-wide association studies of doxorubicin-induced arrhythmia identifies
Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Anthracyclines are a widely used and effective class of chemotherapy. However, a major limitation for their use is cardiotoxicity, manifesting as systolic dysfunction, congestive heart failure (HF) and arrhythmias. Objective: Identify genes and genetic risk variants for doxorubicin-induced arrhythmia. Methods: We performed genome-wide association studies (GWAS) and meta-analysis across two independent non-overlapping, genetically homogenous datasets from the Molecular Epidemiology Resource (MER, cases N=77, controls, N=1,184) and Tapestry, (cases N=13, controls, N=172). Doxorubicin-related arrhythmia was the primary cardiac outcome followed by investigation of a broader phenotype of cardiac events. Effects of doxorubicin on top associated genes were assessed by qPCR on RNA extracted from human cardiomyocytes following treatment with doxorubicin and by echocardiography in a zebrafish model of doxorubicin-induced cardiomyopathy. Results: In the meta-analysis, Conclusions: Genetic variants at
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