particularly for fetally enriched isoforms.26 It is also relevant that splice variants are being recognized as showing functional and therapeutically relevant differences from the canonical isoform,43–45 including examples from other schizophrenia-associated genes,39,46 and being mediated by various molecular mechanisms.44,47,48 As well as having an effect in fetal brain, rs1344706 also influenced expression within a diagnostic group, namely ZNF804AE3E4 mRNA in bipolar disorder. The latter was not a planned analysis and hence the finding is preliminary, but it is notable that, as in fetal brains, the risk allele is associated with lower expression. The mechanism is unclear; presumably, rs1344706 interacts with other bipolar disorder–specific factors (whether genetic, epigenetic, or epiphenomenal) to modulate ZNF804A expression.
