For all 4 co-diagnoses, we found that the HRR increased with higher polygenic loads and was statistically significant for the 10th PRS decile compared to the middle deciles (Figure 5 Extended Data Figure 6-9 and Supplementary Table S19-S22). This was the case for both the single-disorder PRSs and (more strongly) for the aggregate (SUM)PRSs. Similarly, the absolute risk trajectories showed significant differences across deciles for all co-diagnoses, most considerably for bipolar disorder and SUD with absolute risks for the 10th aggregate PRS decile reaching 13% and 21%, respectively, representing a 3.25 (bipolar disorder) and 5.25 (SUD) fold increase in risk compared to the least burdened (1st decile) case groups.
