Fig. 2: Germline predisposition to CH.

a, Within the UKBB, we identified 14 cancer predisposition genes that were associated with CH-heme (red) or mCA-auto (blue). Data are presented as OR (dot) ± 95% CI (whiskers). Black diamonds indicate ORs and 95% CIs from a fixed-effects meta-analysis in our replication cohorts, which include the All of Us (n = 192,003), MGBB (n = 49,941), the Washington University CCDG (n = 37,184), TCGA (n = 7,161) and MSK-IMPACT (n = 17,016) cohorts. b, Heatmap showing the log(OR) within the UKBB between CH-heme in specific genes and germline genes that were statistically significantly (FDR-corrected P < 0.05) associated with higher risk of overall CH-heme. c, Heatmap showing the log(OR) between specific mCA-auto types and germline genes that significantly increased overall mCA-auto. The color scale is the same for b and c. Pair-wise associations that were statistically significant (P < 0.05, two sided with no correction for multiple testing) are shown in the black box in our replication cohort (solid line) and those that were directionally consistent (dashed line). For all analyses, the OR for CH was calculated using multivariable, Firth’s bias-reduced, logistic regression comparing germline carriers with individuals without germline variants, adjusted for age at blood draw, the first three genetic PCs and exome sequencing batch. *q (FDR-corrected P) < 0.05, **q < 0.01, ***q < 0.001.