We investigated various issues pertaining to PTSD-PRS. First, we discussed its opportunities and limitations from a theoretical performance analysis. Next, we constructed the PRS using GWAS summary statistics in a deeply phenotyped and well-curated cohort comprised of OIF/OEF veterans conducted by Systems Biology PTSD Biomarkers Consortium (SBPBC), hereafter referred to as the SysBio cohort. We then showed that ancestral makeup similarity between discovery and validation cohorts was a major performance determinant. Furthermore, as a demonstration of genetic overlap among psychiatric illnesses, we use schizophrenia GWAS summary statistics to predict PTSD phenotypes. Overall, in addition to theoretical and empirical investigation of PRS prediction performance on PTSD onset and severity, we demonstrated its use in studying genetic correlation with other psychiatric disorders.
