  Although displaying genetic correlations, psychiatric disorders are
clinically defined as categorical entities as they each have distinguishing
clinical features and may involve different treatments. Identifying
differential genetic variations between these disorders may reveal how the
disorders differ biologically and help to guide more personalized treatment.
  Here we presented a comprehensive analysis to identify genetic markers
differentially associated with various psychiatric disorders/traits based on
GWAS summary statistics, covering 18 psychiatric traits/disorders and 26
comparisons. We also conducted comprehensive analysis to unravel the genes,
pathways and SNP functional categories involved, and the cell types and tissues
implicated. We also assessed how well one could distinguish between psychiatric
disorders by polygenic risk scores (PRS).
  SNP-based heritabilities (h2SNP) were significantly larger than zero for most
comparisons. Based on current GWAS data, PRS have mostly modest power to
distinguish between psychiatric disorders. For example, we estimated that AUC
for distinguishing schizophrenia from major depressive disorder (MDD), bipolar
disorder (BPD) from MDD and schizophrenia from BPD were 0.694, 0.602 and 0.618
respectively, while the maximum AUC (based on h2SNP) were 0.763, 0.749 and
0.726 respectively. We also uncovered differences in each pair of studied
traits in terms of their differences in genetic correlation with comorbid
traits. For example, clinically-defined MDD appeared to more strongly
genetically correlated with other psychiatric disorders and heart disease, when
compared to non-clinically-defined depression in UK Biobank.
  Our findings highlight genetic differences between psychiatric disorders and
the mechanisms involved. PRS may aid differential diagnosis of selected
psychiatric disorders in the future with larger GWAS samples.
