TY - JOUR
T1 - Analysis of the VAV3 as candidate gene for schizophrenia
T2 - Evidences from voxel-based morphometry and mutation screening
AU - Aleksic, Branko
AU - Kushima, Itaru
AU - Hashimoto, Ryota
AU - Ohi, Kazutaka
AU - Ikeda, Masashi
AU - Yoshimi, Akira
AU - Nakamura, Yukako
AU - Ito, Yoshihito
AU - Okochi, Tomo
AU - Fukuo, Yasuhisa
AU - Yasuda, Yuka
AU - Fukumoto, Motoyuki
AU - Yamamori, Hidenaga
AU - Ujike, Hiroshi
AU - Suzuki, Michio
AU - Inada, Toshiya
AU - Takeda, Masatoshi
AU - Kaibuchi, Kozo
AU - Iwata, Nakao
AU - Ozaki, Norio
PY - 2013/5
Y1 - 2013/5
N2 - 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.
AB - 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.
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U2 - 10.1093/schbul/sbs038
DO - 10.1093/schbul/sbs038
M3 - Article
C2 - 22416266
AN - SCOPUS:84876548631
SN - 0586-7614
VL - 39
SP - 720
EP - 728
JO - Schizophrenia Bulletin
JF - Schizophrenia Bulletin
IS - 3
ER -