Identification of CH genes associated with high risk of hematologic malignancy. (A) We evaluated 166 genes representing the union of 99 genes previously implicated in hematologic malignancy (CH-PD, M-CHIP, and L-CHIP)10,28 and 131 genes mutated at least 40 times in our dataset (observed in ≥∼1 per 1000 individuals). We built cause-specific Cox hazard models with Firth penalized likelihood including adjustments for gender, age, and solid cancer type for all genes and identified 9 with significantly increased hazard rate of hematologic malignancy based on false discovery rate (FDR) < 0.1. (B) HR and 95% CI for high risk CH genes (red, top) and selected comparators that did not meet high risk criteria (blue, bottom). (C) MCAs were divided into an alarm group involving 5/7/17 and an “other” group that did not involve these chromosomes. HRs for MCAs were calculated using the same models described earlier.