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.all_eqtl_w_ase.txtAll eQTLs using total expression onlyall tested SNP-gene pairs using total expression model (suez) only. p_geno is the p-value for a marginal effect eQTL, p_interact for a response-eQTL.all_eqtl.txt.gzall_splicing_qtl.txtall tested SNP-intron pairs. Columns are analogous to all_eqtl.txt.gz.Sample meta datameta data associated with each sample, and columns: * **id** - unique ID for sample. Composed of sample number, cell line, and dosage information. * **sample** - sample number. Range from 1-230. Each set of 5 are the treatments for one individual, in increasing concentrations of dox. * **cell_line** - the cell line number. Each cell line corresponds one individual. * **dbgap** - anonymized ID for matching cell_line to genotypes. * **sample_id** - anonymized ID assigned to each unique combination of `dbgap` and `dosage. * **dosage** - the concentration of dox used in the treatment. * **rin** - the RNA Integrity Number (RIN). Range from 1-10. * **rna_conc** - the RNA concentration (ng/uL) after RNA extraction. * **lib_prep_batch** - the batches the libraries were prepared in. * **index** - the TruSeq adapter index used for multiplexing. * **library_conc** - the concentration (ng/uL) of the library measured on the Bioanalyzer. * **fragment_size** - the mean fragment size as measured on the Bioanalyzer. * **qpcr** - the library concentration (nmol) as measured via qPCR. * **qpcr_dilute** - the concentration (nmol) of the diluted library. * **master_mix** - the master mix for pooling libraries. 10 samples (2 individuals) per master mix. * **lane_perc** - The percentage of sequences in one lane that were assigned to a sample.annotation.txtembryoid_stainingiPSC quality control. This represents a superset of the lines differentiated into cardiomyocytes.leafcutter_counts.txtLeafCutter alternative splicing quantification on all samples.leafcutter_samplesthe rows of this table correspond to the columns of leafcutter_counts.txt.gzlog2_counts_per_million.txtgene expression quantification for 217 samples with >10M exonic reads in our dataset.purityFACS measurements of cardiomyocyte purity, columns are: * cell_line - the cell line number. Each cell line corresponds one individual. * dbgap - anonymized ID for matching cell_line to genotypes. * flow_date - date of flow cytometry experiment * purity - percentage of cells that expressed cardiac troponin (cTnI and cTnT)rarg_trans_eqtl.txttrans eQTL for the rs2229774 non-synonymous variant in RARG. p_geno: marginal effect eQTL p-value. p_interact: response eQTL p-value. Columns starting "q_" correspond to Benjamini-Hochberg adjusted p-values.sample_tablehe rows of this table correspond to the columns of log2_counts_per_million.txt.g