Association of common variants in H2AFZ gene with schizophrenia and cognitive function in patients with schizophrenia

Recently, the H2AFZ gene was reported in relation to schizophrenia in Japanese males. A two-stage case-control study was designed to investigate the association of the H2AFZ gene with schizophrenia and its relationship with cognitive function in Han Chinese patients with schizophrenia. This study included a testing set with 1115 patients and 2289 controls and a validation set with 1843 patients and 3155 controls. A total of 10 single-nucleotide polymorphisms (SNPs) in the H2AFZ gene were genotyped, and both independent data sets were analyzed in association with SNP and gender. The rs2276939 SNP was found to be significantly associated with schizophrenia, particularly in males. A similar pattern was observed in our two-stage study on conducting further imputation and haplotype association analyses. In addition, two of the SNPs (rs61203457 and rs2276939) and cognitive functioning were found to interact significantly when processing the perseverative error in the Wisconsin Card Sorting Test. Our findings suggest that the H2AFZ gene may confer a risk for schizophrenia and contribute to the impairment of executive function in Han Chinese patients with schizophrenia. These findings augment our current state of knowledge regarding the risk of schizophrenia and the impairment of cognitive performance in patients with this disorder.