We used multi-trait conditional and joint analysis (mtCOJO)30 to address the genetic relationship between PTSD and other major mental disorders in two ways. First, we conditioned PTSD PCL-Total on a single mental disorder; then, we conditioned PTSD PCL-Total on all eight mental disorders simultaneously: autism spectrum disorder, major depression, anorexia nervosa, anxiety (case-control), alcohol dependence, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder31–38. The result of this analysis is treated as genetic signal attributable to PTSD in the absence of shared genetic liabilities of other mental disorders. PCL-Total remained highly genetically correlated with the unconditioned GWAS when conditioned on genetically correlated psychiatric disorders independently (i.e. PTSD PCL-Total conditioned on MDD) and simultaneously (i.e., PTSD PCL-Total conditioned on all eight mental disorders; Fig. 5). Conditioning on all eight mental disorder traits significantly reduced the observed-scale SNP-heritability (h2) of PCL-Total (PCL-Total original h2 = 9.21%, P = 1.39 × 10−67; PCL-Total conditioned h2 = 4.11%, P = 2.61 × 10−52) relative to the unconditioned GWAS (Pdifference = 1.52 × 10−13), but this reduction in heritability did not significantly alter associations with biological
