Differences in year of birth and gender across MDD cases and controls were tested using Wilcoxon-Mann-Whitney and chi-square statistics. Cross-correlations between GPRS were evaluated with Pearson’s coefficient. The association of GPRS with MDD (subtypes) was estimated by (multivariate) logistic regressions with controls as the reference category. The proportion of variance explained by GPRS on the liability scale for MDD (subtypes) was estimated using the R2 coefficient proposed by Lee at al.(39), which is directly comparable with heritability and robust against ascertainment bias. Linear transformation on the liability scale was based on prevalence (K) of 0.18 for MDD (Dutch lifetime prevalence(40)); Ks for subtypes were empirically derived based on subtypes proportions among cases. In order to examine the overlap between subtypes obtained with different sub-phenotyping strategies, the performance of appetite/weight subtypes to predict the corresponding LCA-subtypes (decreased appetite/weight→typical and increased appetite/weight→atypical) was evaluated using receiver operating characteristic (ROC) analyses. All analyses were performed with SAS (v. 9.2, SAS Institute, Inc., Cary, NC) and R (v. 3.0.1, R Project for Statistical Computing). Finally, the total variance in liability to MDD (subtypes) explained
