a. Effect of CHIP on the risk of AD in those with APOE ε3ε3 genotype from the ADSP. OR, CI95 and two-sided Wald P value were calculated from a logistic regression model that also included age at the time of blood draw and sex as covariates (Supplementary Table 5 for full regression results). People, n = 2,550. b, Fixed-effect meta-analysis for risk of AD in CHIP carriers using logistic regression in ADSP, FHS and CHS with two-sided Wald P value shown. c, MR for risk of AD based on genetic risk of CHIP using the weighted median estimator on summary statistics from Schwartzentruber et al.18 AD GWAS and GWAX, Finngen AD GWAS and Gr@ACE AD GWAS, which were meta-analyzed using a fixed-effects model. OR, CI95 and two-sided Wald P values for risk of AD per 1 log-odds increase in genetic risk of CHIP are shown. The GWAX analysis was one-sample MR (both CHIP and AD effect estimates were derived from UK Biobank data), while the other studies were two-sample MR. People, n = 692,045. d, Effect of CHIP on the risk of increased CERAD neuritic plaque score in ADSP participants without a dementia diagnosis. OR and CI95 were calculated from an ordinal logistic regression model, which included age at autopsy, APOE genotype, sex and CHIP status as covariates. Two-sided P values were calculated by comparing the t-statistic for each covariate against a standard normal distribution. Full regression results are in Supplementary Table 9. People, n = 427. e, Effect of CHIP on the risk of increased Braak stage in ADSP participants without a dementia diagnosis. OR and CI95 were calculated from an ordinal logistic regression model, which included age at autopsy, APOE genotype, sex and CHIP status as covariates. Two-sided P values were calculated by comparing the t-statistic for each covariate against a standard normal distribution. Full regression results are in Supplementary Table 9. People, n = 454. For all forest plots, the measure of center is the OR and the lines represent the CI95 for the OR.