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

Branko Aleksic, Itaru Kushima, Ryota Hashimoto, Kazutaka Ohi, Masashi Ikeda, Akira Yoshimi, Yukako Nakamura, Yoshihito Ito, Tomo Okochi, Yasuhisa Fukuo, Yuka Yasuda, Motoyuki Fukumoto, Hidenaga Yamamori, Hiroshi Ujike, Michio Suzuki, Toshiya Inada, Masatoshi Takeda, Kozo Kaibuchi, Nakao Iwata, Norio Ozaki

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13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)720-728
Number of pages9
JournalSchizophrenia Bulletin
Volume39
Issue number3
DOIs
Publication statusPublished - 05-2013

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health

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    Aleksic, B., Kushima, I., Hashimoto, R., Ohi, K., Ikeda, M., Yoshimi, A., Nakamura, Y., Ito, Y., Okochi, T., Fukuo, Y., Yasuda, Y., Fukumoto, M., Yamamori, H., Ujike, H., Suzuki, M., Inada, T., Takeda, M., Kaibuchi, K., Iwata, N., & Ozaki, N. (2013). Analysis of the VAV3 as candidate gene for schizophrenia: Evidences from voxel-based morphometry and mutation screening. Schizophrenia Bulletin, 39(3), 720-728. https://doi.org/10.1093/schbul/sbs038