Mean corpuscular volume - median (IQR), fl Neutrophil count (×10 9 cells/l) - median (IQR) White blood cell count (×10 9 cells/l) - median (IQR) Model performance was evaluated by using receiver-operating-characteristic (ROC) analysis and model concordance (c-index). 25, 26 Summed variable weights determined the CHRS values, which were used to define low-, intermediate-, and high-risk groups. Regression models were adjusted for smoking status and cancer history, both independent risk factors for MN. Variables identified by RP analysis were then used in multivariable Cox models to generate statistical weights. Additional information on the RP method, including all variables used, is available in the Supplemental Methods. For patients with CHIP/CCUS in the UKB with at least 10 years of follow-up (n=10,559), conditional probability–based recursive partitioning (RP) analysis was performed by using the rpart package ( ) and minimal complexity pruning with incident MN within 10 years as the single binary outcome. Prognostic model derivation was performed by using a two-stage approach. Additional details on molecular analyses are available in the Supplemental Methods.

15 Lymphoid-specific mCAs were not analyzed. 23 For this study, mCA refers to myeloid mCA and “ambiguous” mCA that were common to both myeloid and lymphoid malignancy. Returned single nucleotide polymorphism (SNP) array data (“Return 3094”) 20, 21 were used to independently annotate mosaic chromosomal abnormalities (mCAs) using estimated break points and relevance to hematologic malignancies according to the cBioPortal for Cancer Genomics 22 and the Atlas of Genetics and Cytogenetics in Oncology and Haematology.

Of the 438,890 individuals eligible for study, 193,743 were used for model derivation and 245,147 were used for validation (Fig.

19 Individuals with low abundance clones (defined by a VAF <0.02), missing laboratory values, and myeloid malignancy preceding or within 6 months of study enrollment were excluded from the analysis. 2, 17, 18 A list of included genes and average coverage per gene has been published previously. Detection of somatic variants in whole-exome sequencing was as previously described, 15 and pathogenic somatic variants in at least one gene associated with CH or myeloid malignancy were used to define CH. UKB 16 data were extracted under application 50834 from a cohort of 502,490 participants 40 to 70 years of age recruited between 20.

The gene siddhartha