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The single-nucleotide polymorphism rs1344706 within the second intron of ZNF804A shows robust association with schizophrenia,1, 2, 3, 4, 5 but does not have an obvious effect on protein coding sequence. Although this could reflect linkage disequilibrium with the actual causal variant(s), re-sequencing and detailed association analyses of ZNF804A in the largest sample to date have not uncovered a variant that is more strongly associated. Given its intronic location, any functional effects of this single-nucleotide polymorphism are likely to be at the level of transcription or splicing, a hypothesis supported by reports of association between rs13344706 and ZNF804A RNA expression. However, additional tests of ZNF804A allelic expression carried out in one of these studies2 suggest that the association with ZNF804A expression may not be directly attributable to this single-nucleotide polymorphism, or that other variants are also involved.

Allelic differences in nuclear protein binding at a genome-wide significant risk variant for schizophrenia in ZNF804A