Although the evidence for association of ZNF804A with SZ remains compelling, the function of the gene is still unknown. The gene is known to be expressed in the brain (Hawrylycz et al., 2012), and is predicted to encode a 1210 amino acids protein, containing a C2H2-type motif. This DNA-binding domain is characteristic of the zinc-finger protein family, thus suggesting a role of ZNF804A in the regulation of gene expression in brain (Donohoe et al., 2010). Moreover, the molecular mechanisms by which rs1344706 increases disease risk have yet to be determined. The SZ associated A allele of rs1344706 appears to correlate with reduced binding affinity for unidentified nuclear protein(s) in neural cells (Hill and Bray, 2011). The A-risk allele has been associated with a higher ZNF804A allelic expression in adult human brain, but does not seem to be the expression quantitative trait loci (eQTL) directly responsible. The association might be through additional cis-regulatory variants that are in high LD with the expressed SNPs rs4667001 or rs12476147 (Hill and Bray, 2012; Williams et al., 2011).
