We leveraged the Psychiatric Genomic Consortium (PGC) GWAS of major depression (MD)33 to generate polygenic risk scores (PRS) in Yale-Penn participants of European descent (N = 3,407). We focused our attention on MD because of the consistent genetic overlap of this trait with suicidality4,7,8. Due to the data sharing restrictions of the 23andMe personal genomics and biotechnology company (a contributor to the PGC MD cohort), GWAS data were publicly available only for a sample subset (59,851 MD cases and 113,154 controls). This analysis was restricted to the participants of genetically confirmed European descent due to known biases of cross-ancestry PRS analysis34. The MD PRS was calculated using PLINK 1.919, considering multiple association P-value thresholds (PT < 5 × 10−8, 10−7, 10−6, 10−5, 10−4, 0.001, 0.05, 0.1, 0.3, 0.5, 1) for SNP inclusion to identify the best-fit for each target phenotype tested. The PRS were calculated after using P-value-informed clumping with a LD cut-off of R2 = 0.3 within a 500 kb window and excluding the major histocompatibility complex region of the genome because of its complex LD structure. The individual
