title: 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.
authors.affiliation: Department of Psychiatry, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Branko
authors.initials: B
authors.lastname: Aleksic
authors.forename: Itaru
authors.initials: I
authors.lastname: Kushima
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ohi
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshimi
authors.forename: Yukako
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ito
authors.forename: Tomo
authors.initials: T
authors.lastname: Okochi
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fukuo
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Fukumoto
authors.forename: Hidenaga
authors.initials: H
authors.lastname: Yamamori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Michio
authors.initials: M
authors.lastname: Suzuki
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics / Q000523:psychology; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D009929:Organ Size; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D013702:Temporal Lobe / Q000473:pathology
chemical_list: D051567:Proto-Oncogene Proteins c-vav; C496621:VAV3 protein, human