These findings advance our understanding of the genetic basis of PTSD, but they also demonstate that PGC-PTSD remains under-powered for the detection of most risk loci and associated pathways. PTSD is similar to major depression in both prevalence (among trauma-exposed persons) and in heritability. There are now 100 genome-wide significant signals for major depression; notably, that level of discovery required 246,363 cases and 561,190 controls27. Other limitations include the treatment of PTSD as a binary disorder in our analysis. Extensive epidemiologic work has shown that subthreshold PTSD is highly prevalent and debilitating65,66. In our analysis, persons with subthreshold PTSD are classified as controls, which would likely reduce our power to find genetic associations. In future work, we will consider PTSD as a continuous phenotype as well as examine clusters of PTSD symptoms, which are more homogeneous. Of note, Gelernter et al. (2019) recently found multiple genome-wide significant loci for re-experiencing symptoms, which is the cluster of symptoms most unique to PTSD, in data from over 100,000 veterans in the Million Veteran Program9. Finally, we used mostly unscreened controls, but controls
