A comprehensive analysis of GSK3B variation for schizophrenia in Han Chinese individuals.

Abstract

Glycogen synthase kinase-3B (GSK-3B) is thought to be involved in numerous neuronal functions and is implicated in the pathophysiology of schizophrenia. Interestingly, a functional polymorphism, rs3755557, in the GSK3B promoter region has been consistently reported to be a risk factor for schizophrenia in southwestern and northwestern Han Chinese individuals. In this study, we carried out a comprehensive analysis of the association of the rs3755557 polymorphism within GSK3B and schizophrenia in Han Chinese individuals. We recruited 782 patients with schizophrenia and 807 healthy controls from eastern China. In total, 143 drug-naïve patients with first-episode schizophrenia were enrolled for the evaluation of clinical features. We did not observe significant differences in genotype or allele distribution of the rs3755557 polymorphism between the schizophrenia and control groups in eastern Chinese individuals. After pooling these data of 2188 subjects with schizophrenia and 2885 healthy controls, we observed a significant difference in the A allele distribution of the rs3755557 polymorphism between schizophrenia patients and controls (Z\u202f=\u202f4.13 P\u202f<\u202f0.01). We further examined the relationship between the rs3755557 polymorphism and the clinical features of schizophrenia by comparing scores of the The Positive and Negative Syndrome Scale (PANSS) and The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) with the genotypes of the rs3755557 polymorphism. There were significant differences in the scores of RBANS attention, delayed memory and total scores between the patients with the A allele and those without the A allele (P\u202f=\u202f0.03, 0.01 and 0.01 after Bonferroni correction, respectively). Our eQTL analysis showed a significant association between the rs3755557 polymorphism and GSK3B expression in the hippocampus (P\u202f=\u202f0.027). Our findings indicated that the rs3755557 polymorphism may confer susceptibility to schizophrenia and cognitive dysfunction in Han Chinese individuals.