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- Title
The impact of the genome-wide supported variant in the cyclin M2 gene on gray matter morphology in schizophrenia.
- Authors
Kazutaka Ohi; Ryota Hashimoto; Hidenaga Yamamori; Yuka Yasuda; Michiko Fujimoto; Satomi Umeda-Yano; Masaki Fukunaga; Yoshiyuki Watanabe; Masao Iwase; Hiroaki Kazui; Masatoshi Takeda
- Abstract
Background Genome-wide significant associations of schizophrenia with eight SNPs in the CNNM2, MIR137, PCGEM1, TRIM26, CSMD1, MMP16, NT5C2 and CCDC68 genes have been identified in a recent mega-analysis of genome-wide association studies. To date, the role of these SNPs on gray matter (GM) volumes remains unclear. Methods After performing quality control for minor-allele frequency > 5% using a JPT HapMap sample and our sample, a genotyping call rate > 95% and Hardy-Weinberg equilibrium testing (p > 0.01), five of eight SNPs were eligible for analysis. We used a comprehensive voxel-based morphometry (VBM) technique to investigate the effects of these five SNPs on GM volumes between major-allele homozygotes and minor-allele carriers in Japanese patients with schizophrenia (n = 173) and healthy subjects (n = 449). Results The rs7914558 risk variant at CNNM2 was associated with voxel-based GM volumes in the bilateral inferior frontal gyri (right T = 4.96, p = 0.0088, left T = 4.66, p = 0.031). These peak voxels, which were affected by the variant, existed in the orbital region of the inferior frontal gyri. Individuals with the risk G/G genotype of rs7914558 had smaller GM volumes in the bilateral inferior frontal gyri than carriers of the non-risk A-allele. Although several effects of the genotype and the genotype-diagnosis interaction of other SNPs on GM volumes were observed in the exploratory VBM analyses, these effects did not remain after the FWEcorrection for multiple tests (p > 0.05). Conclusions Our findings suggest that the genetic variant in the CNNM2 gene could be implicated in the pathogenesis of schizophrenia through the GM volumetric vulnerability of the orbital regions in the inferior frontal gyri.
- Subjects
SCHIZOPHRENIA; SINGLE nucleotide polymorphisms; GENOMES; GENETIC polymorphisms; PSYCHOSES
- Publication
Behavioral & Brain Functions, 2013, Vol 9, Issue 1, p1
- ISSN
1744-9081
- Publication type
Article
- DOI
10.1186/1744-9081-9-40