Further identification of PTSD genetic loci will provide therapeutic insights81. We explored whether genes targeted by specific drugs (and drug classes) were enriched for GWAS signal. These analyses provided tentative support for antipsychotics and opioid drugs – known psychiatric drug classes – and were driven by gene-wise associations with DRD2 (antipsychotics) and CYP2D6 (opioids). Atypical antipsychotics may have efficacy in treating severe PTSD, but otherwise their use is not supported82. Similarly, whereas some observational studies find that chronic opioid use worsens PTSD outcomes83, there is preclinical work motivating the further study of opioid subtype-specific targeting (e.g., partial MOR1 agonism, κ-type opioid receptor [KOR1] antagonism) in the treatment of comorbid PTSD and opioid use disorders84. Analyses in better-powered datasets may identify drug repositioning opportunities and could use the predicted effect of associated variants on gene expression to indicate whether drug candidates would be beneficial or contraindicated in people with PTSD.
