Association of genetic variations in DTNBP1 with cognitive function in schizophrenia patients and healthy subjects.

The dystrobrevin-binding protein 1 gene (DTNBP1) has been regarded as a susceptibility gene for schizophrenia. Recent studies have investigated its role on cognitive function that is frequently impaired in schizophrenia patients, and generated inconsistent results. The present study was performed to elucidate effects of genetic variations in DTNBP1 on various cognitive domains in both schizophrenia patients and healthy subjects. Comprehensive neuropsychological tests were administered to 122 clinically stable schizophrenia patients and 119 healthy subjects. Based on positive findings reported in previous association studies, six SNPs were selected and genotyped. Compared to healthy subjects, schizophrenia patients showed expected lower performance for all of the cognitive domains. After adjusting for age, gender, and educational level, four SNPs showed a nominally significant association with cognitive domains. The association of rs760761 and rs1018381 with the attention and vigilance domain remained significant after applying the correction for multiple testing (P < 0.001). Similar association patterns were observed both, in patients and healthy subjects. The observed results suggest the involvement of DTNBP1 not only in the development of attention deficit of schizophrenia, but also in the inter-individual variability of this cognitive domain within the normal functional range.