Polygenic risk scores (PRS)38 were also consistent across target samples. PRS computed in each PGC study using iPSYCH as the training sample were consistently higher in ADHD cases as compared to controls or pseudo-controls (Supplementary Figure 7). Increasing deciles of PRS in the PGC were associated with higher odds ratio (OR) for ADHD (Figure 2). A similar pattern was seen in five-fold cross validation in the iPSYCH cohort, with PRS for each subset computed from the other four iPSYCH subsets and the PGC samples used as training samples (Online Methods; Figure 2). Across iPSYCH subsets, the mean of the maximum variance explained by the estimated PRS (Nagelkerke’s R2) was 5.5% (SE = 0.0012) (Supplementary Figure 8). The difference in standardized PRS between cases and controls was stable across iPSYCH subsets (OR = 1.56, 95% confidence interval [CI]: 1.53 – 1.60; Supplementary Figure 9) and across waves and PGC cohorts (Supplementary Figure 10). These results further support the highly polygenic architecture of ADHD and demonstrate that ADHD risk is significantly associated with PRS in a dose-dependent manner.
