5/Third, explicit modeling of social determinants of health (SDOH) changed calibration and interpretation of genetic risk in AoU: the same genetic percentile could correspond to different predicted prevalences across social strata.

4/Second, predictive performance was strongly disease dependent:
• for asthma, the broader respiratory score performed best and showed stronger cross-ancestry portability
• for CAD and T2D, disease-specific scores remained stronger

3/First, these broader factor-PGS captured reproducible phenomic structure across independent biobanks, even though the latent factor structure itself is not directly transferable across datasets.

🎉New preprint: Phenome-derived polygenic scores and social determinants jointly shape context-dependent disease risk.

We evaluate disease risk along 2 complementary axes:
• how genetic liability is represented
• the social context in which it is expressed