A new risk locus in the ZEB2 gene for schizophrenia in the Han Chinese population

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- Association of genetic risk of rs6755392 in the ZEB2 gene with schizophrenia will provide new avenues for future research.

The ZEB2 gene encodes the Zinc Finger E-box binding protein. As a key regulator of epithelial mesenchymal differentiation, ZEB2 plays an important role in the pathogenesis of cancer, and its high level expression has been observed in glioma patients. Different mutations in this gene have been identified in patients with Mowat-Wilson syndrome. A previous genome-wide association study (GWAS) of schizophrenia conducted in Caucasians has shown a significant association of rs12991836, located near the ZEB2 gene, with schizophrenia. Thus, we conducted a case control study to further investigate whether this genomic region is also a susceptibility locus for schizophrenia in the Han Chinese population. In total, 1248 schizophrenia (SCZ) cases (mean age ± S.D., 36.44 ± 9.0 years), 1344 bipolar disorder (BPD) cases (mean age ± S.D., 34.84 ± 11.44 years), 1056 major depressive disorder (MDD) cases (mean age ± S.D., 34.41 ± 12.09 years) and 1248 healthy control samples (mean age ± S.D., 30.62 ± 11.35 years) were recruited. We genotyped 12 SNPs using the Sequenom MassARRAY platform in this study. We found that rs6755392 showed a significant association with SCZ (rs6755392: adjusted Pallele = 0.016; adjusted Pgenotype = 0.052; OR (95% CI) = 1.201 (1.073 ~ 1.344)). Additionally, two haplotypes (TCTG, TCTA) were also significantly associated with SCZ. This is the first study claiming the association of the genetic risks of rs6755392 in the ZEB2 gene with schizophrenia.