As risk genes for psychiatric disorders are discovered, revealing the mechanism for association becomes important. ZNF804A is typical of many such associations because the risk SNP is noncoding, and without a coding variant in linkage disequilibrium any functionality is likely mediated via an effect on gene expression. A recent study provided initial evidence for this in fetal but not adult brain.25 Our data confirm this observation and, critically, show that the effect of rs1344706 is on ZNF804AE3E4 mRNA rather than on full-length ZNF804A. The primers used in the earlier study amplify both variants, so the present data are both a replication and a clarification. Our finding that a psychosis risk SNP selectively affects expression of 1 transcript variant of a gene adds to an increasing list of such findings36–42 and supports the proposal that this may be a common feature, 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
