Figure 6.

Combining different sources of uncertainty affects PGS CI calibration

We relax the assumption about PGS effect sizes being fixed and allow for error in effect size estimates. We evaluate the empirical coverage of PGS distributions calculated in three different manners: (left) including genotype uncertainty but not effect-size uncertainty, (middle) including only effect-size uncertainty while using dosages without accounting for genotype uncertainty, and (right) based on the posterior distribution of both effect size and genotypes. All plots show one standard error of the mean empirical coverage across 10 independent simulations. We find that when effect sizes are not fixed, both components must be accounted for in order to achieve proper calibration and estimation of accurate individual PGS CI.