Fig. 1: Prevalence and characteristics of CH in middle-aged individuals.

We performed deep targeted sequencing to identify somatic mutations in a custom panel of 54 CH-related genes in 3,692 individuals from the PESA cohort. a, The number of CH driver mutations identified per gene. The values above the bars indicate the percentage of mutations affecting each specific gene. b, The CH prevalence across quartiles of age. c, The number of mutations per individual across quartiles of age. d, The association between advancing age (stratified as quartiles) and CH (analyzed separately as driven by mutations in DNMT3A, TET2 or other genes) based on multivariate logistic regression analyses adjusted for sex. The bars indicate 95% confidence intervals centered in the mean value (square). e, The distribution of mutant clone size in the study population, assessed as VAF. The dashed line shows the 2% VAF threshold most typically used to identify CH. The box shows the 25th (Q1), 50th (median) and 75th (Q3) percentiles of the data. The whiskers represent Q1 − 1.5 × IQR at the minimum and Q3 + 1.5 × IQR at the maximum. f, The prevalence of CH with VAF ≥2% across quartiles of age. g, The association between gene-specific CH and female sex, based on multivariate logistic regression analyses adjusted for age. The bars indicate 95% confidence intervals centered in the mean value (square). h, The CH prevalence across quartiles of age stratified by sex. In b, f and h, CH status in individuals carrying more than one mutation was defined on the basis of the mutation with the highest VAF.