In addition to the influences of genotype, main effects of diagnosis were found. These again primarily affected ZNF804AE3E4 mRNA rather than the full-length transcript. The diagnostic alterations do not appear to be linked directly to the genetic predisposition: the transcripts change in opposite directions in the 2 disorders with which ZNF804A is associated (decreased in schizophrenia, increased in bipolar disorder), and expression is also affected in major depressive disorder, for which there is no significant evidence of association with ZNF804A. The altered expression in the 3 disorders may in part result from antidepressant use (see Results), but this does not substantially explain the findings. We also did not see relationships with other disease-related variables (eg, duration, age at onset). Thus, the explanations for differential expression of ZNF804AE3E4 mRNA in these disorders and the reduction of ZNF804A mRNA in bipolar disorder remain unclear and warrant additional research.
