Extended Data Fig. 4: Extreme organ agers are widespread in the population.

a, Extreme agers were defined as individuals with a 2-standard deviation increase or decrease in at least one age gap. 23% of the individuals (n = 5,676) across the four cohorts were identified as extreme agers. To visualize all extreme agers, age gaps were denoised by setting values below absolute z-score of 2 to zero. Denoised age gaps are shown in the heatmap. b, Extreme ageotypes were defined based on kmeans clustering of individuals based on their denoised age gaps. The mean z-scored age gap per ageotype is shown. c, The percentage of extreme agers is shown across all cohorts. d, A cross-cohort meta-analysis of associations (logistic regression) between extreme ageotypes versus diagnosis of 9 major age-related diseases annotated in at least 2 independent cohorts. Log odds ratios and significance are shown. P-values were Benjamini-Hochberg FDR-corrected. The strongest associations per disease are highlighted with black borders. (See ST9). e, A cross-cohort meta-analysis of associations (linear regression) between organ age gaps versus diagnosis of 9 major age-related diseases annotated in at least 2 independent cohorts. Disease covariate effects and significance are shown. P-values were Benjamini Hochberg FDR-corrected. The strongest associations per disease are highlighted with black borders. (See ST10). Asterisks represent q-value thresholds: *q  <  0.05; **q  <  0.01; ***q <  0.001.