Figure 2: Comparison of T2D PRSs in people of 1KG-EUR-like genetic ancestries across three cohorts.

Comparison of PRSs for association with prevalent T2D status or time-to-onset of incident T2D in participants of 1KG-EUR-like genetic ancestries from the UK Biobank, INTERVAL, and All of Us research program cohorts. In UK Biobank incident and prevalent T2D were analysed separately due to significant difference in phenotype severity (Methods). Analyses of UK Biobank excluded participants used for metaPRS training, and PRSs derived from GWAS performed in UK Biobank samples. The limited number of PRSs tested in UK Biobank compared to INTERVAL and All of Us reflects that the majority of contemporary PRSs utilize GWAS performed in UK Biobank samples for PRS development. PRSs were adjusted for 20 genetic principal components in each cohort prior to model fitting. Diamonds show the odds ratios or hazard ratios, and horizontal bars show the 95% confidence intervals. Odds ratios and hazard ratios are per standard deviation increase in the respective PC-adjusted PRS. Logistic and Cox proportional hazards regressions were adjusted for age, sex, and cohort specific covariates (e.g., assessment centre). Odds ratios and hazard ratios are detailed in Table S6. Details on comparison PRSs are provided in Table S5.