Figure 3 |. Accuracy and properties of rare and common variant polygenic scores.

We identified “reclassified” individuals with adjusted (but not unadjusted) HbA1C above the T2D diagnostic threshold (47.53 mmol/mol) and compared (via a two-tailed Fisher’s exact test) the fraction of “true” cases among such individuals to the number expected by chance (Methods). a, From top, the forest plot shows Fisher’s exact test odds ratios and 95% confidence intervals for polygenic scores constructed from two exome-wide significant rare variant gene-level associations (PIEZO1/G6PD), the best performing (“loose, nested”) rare variant polygenic score (Erythrocytic Genes), a negative control polygenic score that excludes known erythrocytic genes (Glycemic Genes), a previously published common variant polygenic score⁷ (Common Erythrocytic Variants), and a polygenic score that combines rare and common variants (Combined Erythrocytic PGS). The area of each diamond is proportional to the number of individuals in our test sample reclassified by the score. b, Fisher’s exact test odds ratios stratified by ancestry. The area of each diamond is now proportional to the number of individuals in the US population that would be reclassified by the score after scaling the ancestral proportions in our test sample to those estimated for the US (Methods). Due to inadequate data regarding East Asian and South Asian percentages of the US population, “Asian” represents a meta-analysis of the South Asian and East Asian results; Supplementary Table 10 shows PGS performance within each ancestry. Europeans are not displayed due to insufficient data in our test sample. c-f, Histograms display the distribution (in mmol/mol HbA1C) of rare variant (gray) and common variant (colored) polygenic scores for each ancestry.