Schizophrenia is one of major mental diseases plaguing human beings with strong heredity. Multiple schizophrenia risk genes were discovered using genome-wide association study (GWAS), among which ZNF804A has been recently identified to be another schizophrenia risk gene in European populations. However, whether ZNF804A is a risk gene for schizophreniain Chinese populations remains unknown.

In order to clarify the issue, the research group headed by Dr. SU Bing from Kunming Institute of Zoology Chinese Academy of Sciences (KIZ, CAS) did a systematic genetic analysis on two case-control samples of independent Han Chinese (a total of 2,207 participants) from southwesternChina. A total of six single-nucleotide polymorphisms (SNPs) were tested including the key SNP (rs1344706) that showed significant associationwith schizophrenia in European populations and the other fivepromoter SNPs of ZNF804A. Based on the resultsof the association analysis, the research group performed two functionalassays to test the impact of the risk SNP on transcriptionalfactor binding affinity and promoter activity.

The results showed that SNP rs1344706 was not associated with schizophrenia in eitherof the two Han Chinese groups. However, the research groupidentified two ZNF804A promoter SNPs that were significantlyassociated with schizophrenia in both samples, and the significancewas strengthened in the combined samples and further supportedby haplotype analysis. The functional assays demonstrated thatthe risk SNP (rs359895) can influence Sp1 binding affinity,resulting in a higher promoter activity of the risk allele.

The research results suggest that ZNF804A is a common risk gene for schizophreniain world populations and that the newly identified functionalSNP (rs359895) is likely a risk SNP for schizophrenia. The main findings have been published in American Journal of Psychiatry. (http://ajp.psychiatryonline.org/cgi/content/abstract/appi.ajp.2011.11030381v1)