For schizophrenia, the predictive ability is higher, with the current score accounting for 7% of trait variance and an AUC of 0.61, but these values are still far below that needed for an individual’s score to have sufficient signal for interpretation or for clinical utility [57]. There is greater potential for using risk prediction from genetics in schizophrenia, since the heritability of 65–80% [58, 59] is much higher than 37% for major depression [60], but the substantially different disease lifetime risks (< 1% for schizophrenia vs. 15% for major depressive disorder) is also relevant. Even though polygenic scores are not meaningful for general prediction [57], there are points in the clinical care pathway where PRS could be useful in achieving an earlier or a more precise diagnosis. For example, in first-episode psychosis, we have shown that schizophrenia PRS can differentiate schizophrenia from other psychosis diagnoses (Nagelkerke’s R2 of 9% and those in the top quintile of PRS having an approximately 2-fold increased risk of being subsequently diagnosed with schizophrenia) [24]. This is a low predictive ability, but the setting within
