Genomic Approaches to Posttraumatic Stress Disorder: the Psychiatric Genomic Consortium Initiative

摘要

Post-traumatic stress disorder (PTSD) after exposure to a traumatic event is a highly prevalent psychiatric disorder. Heritability estimates from twin studies as well as from recent molecular data (h²SNP) indicate moderate to high heritability, yet robust genetic variants for PTSD have not yet been identified and the genetic architecture of this polygenic disorder remains largely unknown.To date, less than ten large-scale genome-wide association studies (GWAS) of PTSD have been published, with findings that highlight the unique challenges for PTSD genomics, including a complex diagnostic entity with contingency of PTSD diagnosis on trauma exposure, and the large genetic diversity of the study populations.The Psychiatric Genomics Consortium PTSD group (PGC-PTSD) has brought together over 200 scientists with the goal to increase sample size for GWAS and other genomic analyses to sufficient numbers where robust discoveries of molecular signatures can be achieved. The sample currently includes over 32,000 PTSD cases and 100,000 trauma-exposed controls and collection is ongoing. First results found a significant shared genetic risk of PTSD with other psychiatric disorders, and sex-biased heritability estimates with higher heritability in females compared to males.This review describes the scope and current focus of the PGC-PTSD, and its expansion from the initial GWAS group to nine working groups, including epigenetics, gene expression, imaging, and integrative systems biology. We further briefly outline recent findings and future directions of ‘omics-based’ studies of PTSD, with the ultimate goal of elucidating the molecular architecture of this complex disorder to improve prevention and intervention strategies.