Fig. 6: Association of passenger counts with CHIP.
Association of synonymous passenger mutation counts with a presence of CHIP, b number of CHIP clones, and c growth of CHIP clones. Forest plot of odds ratio (OR) with a 95% confidence interval (CI) showing the effects of (inverse rank normalized) synonymous passenger counts on CHIP-related outcomes (listed below in a–c)—models accounted for age at baseline, age2, self-reported sex, self-reported race, body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, cholesterol medication usage, smoking history, hypertension, atherosclerotic cardiovascular disease (ASCVD, including coronary heart disease and/or ischemic stroke), type 2 diabetes (T2D), and batch effects (including ARIC baseline visit and visit center). Uncorrected P-values are from two-sided Z-tests. a Model 1: four separate multivariable logistic regression analyses were performed for outcomes (i) no CHIP (n = 2905) vs. presence of CHIP at either visit (n = 1147), (ii) no CHIP at baseline (n = 3614) vs. CHIP detected at baseline (i.e. prevalent CHIP, n = 438), (iii) no CHIP at follow-up visit (n = 3043) vs. CHIP detected at the follow-up visit (n = 1009), and (iv) no CHIP (n = 2905) vs. incident CHIP (n = 709). b Model 2: multivariable multinomial logistic regression was performed for the number of CHIP clones as outcomes, i.e., no CHIP clone (n = 2905) vs. one clone (n = 877), 2 clones (n = 206), 3 clones (n = 43), or ≥4 clones (n = 21). c Multivariable logistic regression was performed for no CHIP clone (or no change in clone size, dVAF = 0; n = 2909) vs. growing CHIP clone (i.e. dVAF > 0; n = 936). BMI, HDL-C, and non-HDL-C values were inverse rank normalized. CHIP: clonal hematopoiesis of indeterminate potential; dVAF = VAFfollow-up − VAFbaseline.
