Transcriptome-wide association study uncovers the role of essential genes in anthracycline-induced cardiotoxicity.

ABSTRACT: Anthracyclines are highly effective chemotherapeutic agents; however, their clinical utility is limited by severe anthracycline-induced cardiotoxicity (ACT). Genome-wide association studies (GWAS) have uncovered several genetic variants associated with ACT, but the impact of these findings requires further elucidation. We conducted a transcriptome-wide association study (TWAS) using our previous GWAS summary statistics (n = 280 patients) to identify gene expression-related associations with ACT. We identified a genetic association between decreased expression of GDF5 and ACT (Z-score = -4.30, P = 1.70 × 10^-5), which was replicated in an independent cohort (n = 845 patients, P = 3.54 × 10^-3). Additionally, cell viability of GDF5-silenced human cardiac myocytes was sign

SUBMITTER: Scott EN 

PROVIDER: S-EPMC8140137 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature