Large-Scale Genetic Characterization of PTSD Across Ancestry, Gender and Trauma-Type

Abstract

BackgroundDevelopment of post-traumatic stress disorder (PTSD) is influenced by both environmental and genetic factors. In the most current data (freeze 2), the Psychiatric Genomics Consortium (PGC) PTSD group has accumulated over 50 studies with genomic data from over 20,000 PTSD cases and 50,000 trauma-exposed controls. Here we present findings from genome-wide association studies (GWAS) across ancestry groups, gender and trauma-type and present a genetic characterization of PTSD including SNP-based heritability analyses and genetic correlation across psychiatric disorders and other phenotypes / traits of interest. MethodsGenotypes were processed with the PGC-pipeline, modified for ancestry assessment. GWAS were performed within European, African American, and Latino ancestry groups and meta-analyzed across studies and ancestries. Stratified analyses for gender and trauma type were also conducted. Standard methods were used to estimate SNP-based heritability and genetic correlations with other psychiatric disorders and traits in European-ancestry subsets. ResultsStratified analyses showed genome-wide significant hits in the European and African American data, and some evidence for association in the smaller Latino ancestry group. Analyses across ancestry groups did not result in genome-wide significant hits. We will present results extending our findings from the PGC PTSD freeze 1, which found that PTSD liability was significantly influenced by genetics (p<0.05), with SNP-based heritability being higher in European American women (29%, p<0.05) than in men (7%, NS. Polygenic methods consistently show a significant overlap of PTSD with other psychiatric disorders. ConclusionsOur current findings show that PTSD is significantly influenced by genetic factors, which vary between females and males and overlap with other psychiatric disorders. Unique challenges faced by the PGC PTSD group is the wide range of ancestry, high degree of admixed samples, and large number of studies contributing relatively small number of cases. Consistent with findings from other PGC disorders, much larger sample sizes are needed to fully characterize the genetic architecture of PTSD.