dataset (43), leading to smaller sampling variance on the individual SNP effects. For GPRS based on the latest schizophrenia PGC-GWAS(34) the discovery sample size was ~150K samples, whereas this was ~16K for GPRS based on MDD(4) and bipolar disorder(44). In a seminal paper, Dudbrige(43) elegantly showed that the accuracy of GPRS predictions depends on the size of the training samples. Since PGC cross-disorder analyses showed(28) that MDD could be predicted by GPRS for the other psychiatric disorders, we could expect that - due to a training sample that was almost 10-times larger - the schizophrenia GPRS may explain a portion of MDD variance even larger than GPRS for the same trait. Using Dudbrige’s equations(43) estimating the predictive accuracy of GPRS as a function of parameters such as discovery sample size, we confirmed the empirical values of explained variance obtained in the current study. More interestingly, results indicated that the availability of a discovery GWAS for MDD of the same size as that for schizophrenia, may lead to an even larger amount of variance explained in MDD liability by MDD GPRS. These results confirmed that the predictive accuracy of GPRS should be always interpreted in light of the genetic characteristics of
