Datasets related to a study aimed to identify genetic markers of CDA by subphenotypes associated with cardiotoxicity

Here we present a series of supplemental datasets that complement our study entitled "A Systems Genetics approach to identify genetic markers of cardiotoxicity due to anthracyclines in cancer patients." The datasets presented here were used to generate the main and supplementary figures and tables of the indicated study. The study consists of the identification of genetic markers of cardiotoxicity due to anthracyclines (CDA). CDA is a complex genesis disease or complex trait, and because of this, there is a component of missing heritability. Therefore, it is not possible to identify genetic markers associated with CDA risk. Here, we propose that molecular subphenotypes associated with the CDA may be a strategy for identifying some of this missing heritability and risk markers associated with it. A similar strategy could be applied to identify markers of other diseases of complex genesis. This study is done using a genetically heterogeneous cohort of mice that developed breast cancer and was treated with doxorubicin or a combined treatment of doxorubicin and docetaxel. The mouse cohort was generated by backcrossing, so each mouse is genetically unique. Post-chemotherapy heart damage was assessed by quantifying fibrosis's cardiac area and the thickness of myocardial fibers. The genetic regions associated with CDA were assessed by massive genotyping and genetic linkage analysis. Several molecular subphenotypes were quantified in the myocardium, and their association with the CDA was evaluated. Subsequently, we identified which of them were most statistically associated with CDA in multivariate models. Moreover, which complex trait loci (QTLs) associated with molecular subphenotypes best explained CDA. This strategy served to identify in the cohort of mice genes whose allelic forms could be candidates for the risk of CDA. Allelic variants of these genes were evaluated in four cohorts of cancer patients treated with anthracyclines and whose CDA was evaluated by echocardi