Abstract
Recent genome-wide association studies of schizophrenia reported a novel risk variant, rs2312147 at vaccinia-related kinase 2 gene (VRK2), in multiple Asian and European samples. However, its effect on the brain structure in schizophrenia is little known. We analyzed the brain structure of 36 schizophrenia patients and 18 healthy subjects with regard to rs2312147 genotype groups. Brain magnetic resonance scans for gray matter (GM) and white matter (WM) analysis, and genotype analysis for VRK2 rs2312147, were conducted. The Positive and Negative Syndrome Scale and the Digit Symbol Test were assessed for schizophrenia patients. There was no significant difference in either GM volume or WM connectivity with regard to rs2312147 genotype in healthy subjects. In contrast, we found significant differences in the WM connectivity between rs2312147 CC and CT/TT genotype groups of schizophrenia patients. The related brain areas included the splenium of corpus callosum, the left occipital lobe WM, the internal capsule (left anterior limb and right retrolenticular part), the bilateral temporal lobe WM, the left fornix/stria terminalis, the left cingulate gyrus WM, and the left parietal lobe WM. Voxelwise correlation analysis revealed that the Digit Symbol Test scores (age corrected) correlated with the fractional anisotropy in WM tracts that previously showed significant group differences between the CT/TT and CC genotypes in the rs2312147 CT/TT genotype group, while no significant correlation was found in the CC genotype group. Our data may provide evidence for the effect of VRK2 on WM connectivity in patients with schizophrenia.
Highlights
Recent developments in genome sequencing have made schizophrenia a hot topic in the genetics of neuropsychiatry through genome-wide association studies (GWASs)
Conducted GWASs showed the significant association of rs2312147, located about 50 kb upstream of vaccinia-related kinase 2 gene (VRK2), and schizophrenia in Asians [9] as well as Europeans [2,5,10]
We first report a significant association of rs2312147 with the white matter (WM) connectivity in schizophrenia patients
Summary
Recent developments in genome sequencing have made schizophrenia a hot topic in the genetics of neuropsychiatry through genome-wide association studies (GWASs). GWASs and meta-analyses reported a group of common genetic variants significantly conferring the risk of schizophrenia in Europeans [1,2,3,4,5,6,7] and in Chinese [8,9]. Rs2312147 [C], located ,50 kb upstream of vaccinia-related kinase 2 (VRK2), was identified as a novel risk of single nucleotide polymorphism (SNP) associated with schizophrenia in Europeans [2,5,10] and Asians [9]. The function of VRK2 in schizophrenia is not well known, VRK2 rs2312147 C allele was reported to show a significant association with schizophrenia [European combined samples: odds ratio (OR) = 1.09, P = 1.961029 [5]; Asian combined samples: OR = 1.16, P = 4.2461024 [9]]and VRK2 gene expression was up-regulated in the blood cells of patients with schizophrenia [9].
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