Associative Sudy Of ZNF804A Rs1344706Polymorphism And Abnormal White Matter In Schizophrenic Patients

ObjectiveSeveral previous genome-wide association studies have confirmed the association between a single nucleotide polymorphism (SNP) rs1344706in ZNF804A and schizophrenia. The task-independent effects of the risk variant on the functional connectivity prompted the hypothesis that the effect may be mediated by white matter structural connectivity. However, the association between ZNF804A and white matter remains unknown.Methods(1)69healthy controls and80patients with schizophrenia underwent genotyping of rs1344706SNPs, and were examined for white matter density (T1-weighted MRI). The association of rs1344706with white matter changes in schizophrenia patients and healthy controls was analyzed using a full-factorial2×2analysis of variance.(2)100patients with schizophrenia and69healthy controls were genotyped at the SNP rs1344706. Diffusion tensor imaging (DTI) scans of the subjects were analyzed with tract-based spatial statistics (TBSS). Careful statistical analysis with a full-factorial two-way analysis of variance (ANOVA) was conducted on multiple diffusion indices, including fractional anisotropy (FA), axial diffusivity (L1), radial diffusivity components (L2and L3), and mean diffusion (MD).Results(1) There was an interaction on white matter density in the left prefrontal lobe between the rs1344706genotype and schizophrenic diagnosis, where the risk T allele carriers presented higher white matter density in the schizophrenia patients and lower white matter density in healthy controls in comparison with the non-risk allele carriers. The risk allele was associated with an increased white matter density of the bilateral hippocampus in both the patients and the healthy group.(2)Although significant main effects of the diagnosis of schizophrenia were found on L2and L3, no association between the ZNF804A SNP and white matter connectivity was found in the entire group of subjects nor in a selected subgroup (SEL; n=72) of age-matched subjects.ConclusionThe ZNF804A variant may confer risk for schizophrenia by exerting its effects on the white matter density in the left prefrontal lobe together with other risk factors for schizophrenia. However, this gene has no association with white matter fiber tract integrity based on standard DTI methods.