title: The impact of the genome-wide supported variant in the cyclin M2 gene on gray matter morphology in schizophrenia.
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 FWE-correction 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.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ohi
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan. hashimor@psy.med.osaka-u.ac.jp.
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Hidenaga
authors.initials: H
authors.lastname: Yamamori
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Michiko
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Satomi
authors.initials: S
authors.lastname: Umeda-Yano
authors.forename: Masaki
authors.initials: M
authors.lastname: Fukunaga
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Masao
authors.initials: M
authors.lastname: Iwase
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kazui
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D027682:Cation Transport Proteins; D016213:Cyclins / Q000235:genetics*; D005260:Female; D005625:Frontal Lobe / Q000502:physiology*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult
chemical_list: C558175:CNNM2 protein, human; D027682:Cation Transport Proteins; D016213:Cyclins