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Analysis of the VAV3 as candidate gene for schizophrenia: evidences from voxel-based morphometry and mutation screening.

ABSTRACT: In recently completed Japanese genome-wide association studies (GWAS) of schizophrenia (JPN_GWAS) one of the top association signals was detected in the region of VAV3, a gene that maps to the chromosome 1p13.3. In order to complement JPN_GWAS findings, we tested the association of rs1410403 with brain structure in healthy individuals and schizophrenic patients and performed exon resequencing of VAV3. We performed voxel-based morphometry (VBM) and mutation screening of VAV3. Four independent samples were used in the present study: (1) for VBM analysis, we used case-control sample comprising 100 patients with schizophrenia and 264 healthy controls, (2) mutation analysis was performed on a total of 321 patients suffering from schizophrenia, and 2 case-control samples (3) 729 unrelated patients with schizophrenia and 564 healthy comparison subjects, and (4) sample comprising 1511 cases and 1517 healthy comparison subjects and were used for genetic association analysis of novel coding variants with schizophrenia. The VBM analysis suggests that rs1410403 might affect the volume of the left superior and middle temporal gyri (P=.011 and P=.013, respectively), which were reduced in patients with schizophrenia compared with healthy subjects. Moreover, 4 rare novel missense variants were detected. The mutations were followed-up in large independent sample, and one of the novel variants (Glu741Gly) was associated with schizophrenia (P=.02). These findings demonstrate that VAV3 can be seen as novel candidate gene for schizophrenia in which both rare and common variants may be related to increased genetic risk for schizophrenia in Japanese population.

SUBMITTER: Aleksic B

PROVIDER: S-EPMC3627762 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Analysis of the VAV3 as candidate gene for schizophrenia: evidences from voxel-based morphometry and mutation screening.

Aleksic Branko B Kushima Itaru I Hashimoto Ryota R Ohi Kazutaka K Ikeda Masashi M Yoshimi Akira A Nakamura Yukako Y Ito Yoshihito Y Okochi Tomo T Fukuo Yasuhisa Y Yasuda Yuka Y Fukumoto Motoyuki M Yamamori Hidenaga H Ujike Hiroshi H Suzuki Michio M Inada Toshiya T Takeda Masatoshi M Kaibuchi Kozo K Iwata Nakao N Ozaki Norio N

Schizophrenia bulletin 20120313 3

In recently completed Japanese genome-wide association studies (GWAS) of schizophrenia (JPN_GWAS) one of the top association signals was detected in the region of VAV3, a gene that maps to the chromosome 1p13.3. In order to complement JPN_GWAS findings, we tested the association of rs1410403 with brain structure in healthy individuals and schizophrenic patients and performed exon resequencing of VAV3. We performed voxel-based morphometry (VBM) and mutation screening of VAV3. Four independent sam ...[more]

PMID: 22416266

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Project description:BackgroundAging is the most significant risk factor for dementia. Alzheimer's disease (AD) accounts for approximately 60-80% of all dementia cases in older adults. This study aimed to examine the relationship between finger movements and brain volume in AD patients using a voxel-based reginal analysis system for Alzheimer's disease (VSRAD) software.MethodsPatients diagnosed with AD at the Center for Comprehensive Care and Research on Memory Disorders were included. The diagnostic criteria were based on the National Institute on Aging-Alzheimer's Association. A finger-tapping device was used for all measurements. Participants performed the tasks in the following order: with their non-dominant hand, dominant hand, both hands simultaneously, and alternate hands. Movements were measured for 15 s each. The relationship between distance and output was measured. Magnetic resonance imaging measurements were performed, and VSRAD was conducted using sagittal section 3D T1-weighted images. The Z-score was used to calculate the severity of medial temporal lobe atrophy. Pearson's product-moment correlation coefficient analyzed the relationship between the severity of medial temporal lobe atrophy and mean values of the parameters in the finger-tapping movements. The statistical significance level was set at <5%. The calculated p-values were corrected using the Bonferroni method.ResultsSixty-two patients were included in the study. Comparison between VSRAD and MoCA-J scores corrected for p-values showed a significant negative correlation with the extent of gray matter atrophy (r = -0. 52; p< 0.001). A positive correlation was observed between the severity of medial temporal lobe atrophy and standard deviation (SD) of the distance rate of velocity peak in extending movements in the non-dominant hand (r = 0. 51; p< 0.001).ConclusionsThe SD of distance rate of velocity peak in extending movements extracted from finger taps may be a useful parameter for the early detection of AD and diagnosis of its severity.

Dataset Information

Analysis of the VAV3 as candidate gene for schizophrenia: evidences from voxel-based morphometry and mutation screening.

Publications

Analysis of the VAV3 as candidate gene for schizophrenia: evidences from voxel-based morphometry and mutation screening.

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