The main technical challenge in building genomic profiles, besides shortage of study samples, is the fact that the genetic architecture of PTSD, not unlike most other complex psychiatric traits18, is highly polygenic. Individual (or even a few dozen) common SNP variants account for only a small part of the genetic influence. For instance, the largest published PTSD GWAS to date17, done with 20,000 (25% cases) participants, could not find any novel GWAS significant variant, nor could it replicate previously identified hits. A study of this sample size had 80% power to detect a disease (causative) allele with genotype relative risk of 1.186–1.35 (assuming an additive model with disease allele frequency of 5–20% and a prevalence of 8% requiring a significance level of 5e-8). This suggests that common variants have individually small effect-sizes and are not by themselves predictive of PTSD risk.
