The impact of polygenic score and socioeconomic status in predicting risk for 19 complex diseases.

Both socioeconomic circumstances and genetic predisposition shape disease risk, yet their joint contribution across diseases has not been systematically examined. We studied 19 high-burden diseases in 743,194 participants (729,928 European; 13,266 non-European ancestry) from FinnGen, the UK Biobank, and Generation Scotland. Higher educational attainment was associated with lower risk of most conditions, but with higher risk of most common cancers. These associations were largely independent of disease-specific polygenic scores (PGSs). For seven out of 19 diseases, PGSs showed stronger effects among individuals with high education. Joint inclusion of education and PGSs modestly improved prediction for 14 and 10 out of 19 diseases in FinnGen and the UK Biobank, respectively. PGS associations were consistent across ancestries, whereas education effects were less stable; results using an alternative socioeconomic measure were directionally similar but smaller. Our findings highlight the distinct and partly interacting contributions of socioeconomic and genetic factors to disease risk.