OTE-Related Polygenic Analysis

GPSs of OTE were calculated using the “score” command in the PLINK software with reference to Purcell (2009). The reference GWAS statistics were derived from a Big Five personality GWAS meta-analysis published by the Genetics of Personality Consortium (De Moor et al., 2012)⁵. A total of 2.4 M single-nucleotide polymorphisms was found in 10 samples (17,375 adults) and five replicated samples (3,294 adults). From this result, we obtained the effect size of SNP risk alleles (obtained by logarithmic transformation of Odds Ratio value) and the correlation significance (p-value). Then, representative SNPs were selected from each linkage disequilibrium (LD) block, which made the loci included in the calculation of GPSs relatively independent. Finally, different GWAS association significance (p = 0.0001, 0.001, 0.01, 0.05, 0.25, 0.5, 1) was selected, and the risk effects of the corresponding reference sites were multiplied by the number of risk alleles (0, 1, or 2) carried by the subjects to obtain the GPSs under the seven threshold values. Previous studies have shown that a polygenic risk score (PRS) with a threshold of 0.05 generated the highest risk score prediction accuracy (Ripke et al., 2014). Another study also found that PRS6 (p = 0.05) constructed from schizophrenia-related alleles produced the highest risk score with prediction accuracy for hippocampal activity (Chen et al., 2018). Therefore, the GPSs with a threshold of 0.05 were selected for the main results. Other threshold results are shown in Supplementary Materials.