Extended Data Fig. 3: Associations between CH and diseases.

a, Phenome-wide association study of CH and incident disease outcomes. Phenotypes were extracted from the International Classification of Diseases version-10 (ICD-10) disease codes and grouped in different categories. A total of 11,787 ICD-10 codes were tested using logistic regression, obtaining results for 2,378. Risk ratio (RR) of each code is represented by a single point with a size scale. The black dashed line represents the phenome-wide significant P-value threshold of 10⁻⁹. Only ICD-10 codes with false discovery rate (FDR)<10⁻¹⁵ are annotated to control for multiple comparisons. Full results with RRs, 95% confidence intervals (CIs), P-values and FDRs are reported in Supplementary Table 8. b, Heatmaps showing associations of overall CH (CH), CH with large (CH large) and small (CH small) clones, and CH driven by DNMT3A, TET2, ASXL1, JAK2, and SRSF2+SF3B1 mutations with incident hematopoietic neoplasms and cancer in self-reported non-smokers. Red-blue color scale represents the hazard ratio (HR). HRs were calculated using competing risks models. Gray color represents failure of the logistic regression model (maximum likelihood estimation algorithm) to converge. Asterisk represents a significant association, and its size represents different unadjusted P-value cut-offs. All HRs, 95% CIs, sample sizes, P-values, and FDRs (to adjust for multiple comparisons) are reported in Supplementary Table 11. c, Forest plot showing the hazard ratios (HRs) for cardiovascular disease (CVD) from competing risks analysis in CH using four models: univariate with CH as the only predictor, bivariate including CH and smoking status, bivariate with CH and age, and trivariate with CH, smoking status and age. HR markers with unadjusted P<0.05 are depicted in blue. Symbols represent the HRs and error bars represent 95% CIs. All HRs, 95% CIs, sample sizes, P-values, and FDRs (to adjust for multiple comparisons) are reported in Supplementary Table 12. Abbreviations: AML, acute myeloid leukemia; MDS, myelodysplastic syndromes; MPN, myeloproliferative neoplasms; CMML, chronic myelomonocytic leukemia; CVD, cardiovascular disease.