Polygenic risk scores (PGS) analyses were conducted to test the predictive power of the meta-analysis results for neuroticism itself and for MDD. PGS were computed in NTR and Netherlands Study of Depression and Anxiety (NESDA51) and were based on the meta-analysis results excluding the NTR and NESDA cohorts, further referred to as the discovery set. PGS were calculated for all individuals of the NTR and NESDA target set by taking a set of most significant SNPs from the analysis in the discovery set and by multiplying the individual’s genotypic score (0, 1 or 2 for genotyped SNPs, or any value in between 0 and 2 for imputed SNPs) by the effect size of a particular SNP (unstandardized regression coefficient based on the meta-analysis), and summing this over SNPs. PGS were calculated for six different P-value thresholds (P<1 × 10−5, P<1 × 10−4, P<1 × 10−3, P<0.01, P<0.05 and P<0.5). Next, linear/logistic regression was conducted to predict neuroticism from the PGS in 8,648 NTR participants and MDD status in 1,859 unrelated MDD cases and 2,391 unrelated controls from NTR and NESDA.
