Extended Data Fig. 4: Association of CHEK2 and ATM germline carrier status with CH and hematologic malignancies by germline variant type in the UK Biobank.

a. Shown in red and blue are the odds ratios (center dot) and 95% confidence intervals (error bars) for CH-heme and mCA-auto among people with germline CHEK2 loss of function variants, CHEK2 missense variants, ATM loss of function variants or ATM missense variants compared to non-carriers. The odds ratios were calculated using multivariable Firth’s bias-reduced logistic regression adjusted for age at blood draw, the first three genetic principal components, and exome sequencing batch. b. Shown in red and blue are the hazard ratios (center dot) and 95% confidence intervals (error bars) for myeloid and lymphoid malignancies by CHEK2 or ATM germline variant type. The hazard ratios were calculated using Cox regression adjusted for the same covariates as above. The number of individuals for above analyses are as follows: germline CHEK2 loss of function variant carriers (n = 2,670), CHEK2 missense variant carriers (n = 1,318), ATM loss of function variant carriers (n = 1,564) and ATM missense variant carriers (n = 535). *P < 0.05, **P < 0.01, ***P < 0.001. Two-sided P value is not corrected for multiple hypothesis testing. See Supplementary Tables 15, 16 for exact P values.