Fig. 4

Characteristics of prognostic germline variants and improvement of patient outcome models by the prognostic germline variants. a, b Scatterplots of the prognostic germline variants identified in individual cancers in analysis 1 (a) and in groups of cancers in analysis 3 (b). Each pie chart reflects the distribution of patients that are homozygous for the reference allele, heterozygous, and homozygous for the alternate allele for one prognostic variant. The minor allele was much more likely to be associated with increased risk for poor outcome rather than decreased risk for poor outcome (p = 7.077E−8) in analysis 1 though this trend was not significant in analysis 3 (p = 0.115). c, d Pie charts displaying the genomic locations of the germline variants in analysis 1 (c) and analysis 3 (d). e An example of a receiver operator characteristic (ROC) curve calculated using data from LAML at 366 days of follow-up. The blue line represents the patient outcome predictions made using clinical information alone (C model). The red line represents patient outcome predictions made using clinical information in addition to rs3003628 germline variant status (C + GV model), which we found to be predictive of patient outcomes in LAML. The area under the curve (AUC) was 0.81 for the C model and 0.93 for the C + GV model giving a ΔAUC of 0.12 (12%). f Many of the prognostic germline variants improve clinical outcome model predictions. For each prognostic variant, we created a ROC curve based on the clinical (C) model and the clinical + germline variant (C + GV model), as in Fig. 4e, at each point in time from the 10th-90th percentile of patient progression or death for each cancer. The ΔAUC of the C + GV model versus the C model at each time point was calculated (Additional file 3: Table S4). X-axis: Mean and standard error of ΔAUC. Y-axis: The p values from testing whether or not the AUC of the C + GV model is significantly greater than that of the C model using a Wilcoxon rank sum test. Four examples of prognostic germline variants that significantly increase the AUC are labeled and highlighted in Additional file 3: Table S4