Data from: Determining the genetic basis of anthracycline-cardiotoxicity by response QTL mapping in induced cardiomyocytes

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 24h 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 QTLs
and 42 response-splicing QTLs, which are enriched in lower ACT GWAS
p-values, supporting the in vivo relevance of our map of gene tic
regulation of cellular response to anthracyclines.