F92. Polygenic Risk Score from Schizophrenia Predicts PTSD and Depression Symptoms After Trauma Exposure

Abstract

Background: Posttraumatic stress disorder (PTSD) develops in about 10% of those exposed to trauma. Identifying those who develop early symptoms can be a powerful prognostic tool, as early intervention can be crucial for the disease course. Genetic susceptibility is an important risk-factor, but identifying single-nucleotide polymorphisms (SNPs) causal variants has been challenging, highlighting the polygenic architecture of PTSD and its symptoms. Many SNPs of small effect size may be more useful to capture such phenotypes. Polygenic risk score (PRS) from the largest genome-wide association study (GWAS) - the Psychiatric-Genomics Consortium for Schizophrenia (PGC-SCZ) - has shown shared vulnerability across psychiatric disorders, including Schizophrenia, MDD and BP. We aimed to evaluate whether the PRS from PGC-SCZ can predict PTSD, its symptoms, or comorbid depression in subjects assessed longitudinally after trauma-exposure. Method(s): Participants were recruited from the emergency department of a trauma-center and PTSD and depression assessed approximately 1 (n=267), 3 (n=238), 6 (n=197), and 12 (n=173) months after trauma. Genotyping from saliva-DNA collected at each data-point was performed with Psych-Array. Summary statistic from the PGC-SCZ was used to calculate PRS to predict PTSD or depression symptoms at different time points. Result(s): SCZ-PGC was able to highly predict PTSD (r2=6.14% p=7.6x10-7) and depression symptoms (r2=3.96% p=7.6x10-5) at 1 month. Nominal predictions were observed at 3, 6 and 12 months for PTSD, and 6 and 12 months for depression symptoms. Conclusion(s): Transdiagnostic psychiatric vulnerability assessed with PRS successfully predicts patients with distinct PTSD and depression risk and severity levels after trauma exposure and may facilitate early intervention. Supported By: R01 MH094757 "Prospective Determination of Psychobiological Risk Factors for PTSD" Keywords: MDD, PTSD, PRS, SCZCopyright © 2019