Schizophrenia is a severe and complex human mental disorder bothers millions of people world-wild, of which the genetic and environmental factors　play a combinative role in the development, while, although many possible outbreak candidates have been proposed, the underlying genetic risk factors are yet to be identified.

Recently, GSK3β, which is of pivotal importance in brain development and function, has been proved the schizophrenia susceptible gene according to Dr. LI Ming and his colleagues’ research by analyzing 2 550 cases of Chinese population (Kunming Institute of Zoology, CAS).

Not only the proof of GSK3β’s involvement in schizophrenia is inconsistent, but the clarity of its risk genetic variants in schizophrenia is also poor. In this study, Dr. LI and his colleagues conducted an association analysis of 9 representative SNPs spanning the entire genomic region of GSK3β in two independent Han Chinese case–control samples from southwestern China (the Kunming sample and the Yuxi sample, a total of 2550 subjects). The electrophoretic mobility shift assay(EMSA) and reporter gene assays have been adopted to test the functional impact of the identified risk SNP on transcriptional factor binding affinity and promoter activity. The weak allelic associations of three GSK3β SNPs (rs3755557, rs7431209 and rs13320980) with schizophrenia in the combined Han Chinese samples have been observed. Analysis using genotypes (under recessive genetic models) also supported the association of rs3755557.

Consistent with previous results derived by overexpressing GSK3β in mice, Dr. Li’s findings suggest the risk SNP (rs3755557) could influence the transcription factor binding affinities, resulting in a higher promoter activity of the risk allele and that GSK3β is likely a risk gene for schizophrenia, and its expression alteration caused by the risk SNP in the promoter region may contribute to the etiology of schizophrenia.

The main findings have been published in Schizophrenia Research (doi:10.1016/j.schres.2011.09.013)