# Stratified LD Score Regression

Complex-disease risk often acts through regulatory programs that appear only after a cell is perturbed, and steady-state molecular atlases capture them poorly. Perturbscape couples multiscale gene programs learned for each perturbation in CRISPR Perturb-seq screens with human genetics, evaluated across 15,859 perturbation-by-context profiles from 7 Perturb-seq systems and 53 diseases and traits. Perturbation-induced programs reached up to 4.3-fold higher heritability informativeness than steady-state multi-tissue gene prioritization and retained significant conditional heritability informativeness in all 34 matched cell system–trait comparisons after accounting for steady-state prioritization.

Complex-disease risk often acts through regulatory programs that appear only after a cell is perturbed, and steady-state molecular atlases capture them poorly. Perturbscape couples multiscale gene programs learned for each perturbation in CRISPR Perturb-seq screens with human genetics, evaluated across 15,859 perturbation-by-context profiles from 7 Perturb-seq systems and 53 diseases and traits. Perturbation-induced programs reached up to 4.3-fold higher heritability informativeness than steady-state multi-tissue gene prioritization and retained significant conditional heritability informativeness in all 34 matched cell system–trait comparisons after accounting for steady-state prioritization.