To investigate whether PRS can prospectively predict recurrence among individuals with first-onset depression, we performed Cox’s regression analyses estimating hazard rate ratio (HRR) and absolute risk of developing a second episode of depression over time among individuals having a first diagnosis of depression in a hospital. This was done for groups with higher polygenic load, in PRS deciles. We found that the HRR of developing a second-episode generally increased with higher depression-PRS, most significantly for the 10th DEP-PRS decile with HRR10/1=1.33 (SE=0.06, P=2.5 x 10−6) when compared to the first decile and HRR10/middle=1.14 (SE=0.04, P=0.001) or compared with the middle (2nd-9th) deciles (Figure 5, Supplementary Figure S17-1 and Table S17A). Similarly, the absolute risk of a second diagnosis of depression increased with time since the first diagnosis for all depression-PRS deciles, with the trajectories for the 10th decile reaching an absolute risk of 38% compared to 29% and 33% for lowest and middle deciles, respectively (Figure 5).
