title: The polymorphism of YWHAE, a gene encoding 14-3-3epsilon, and brain morphology in schizophrenia: a voxel-based morphometric study.
abstract: BACKGROUND
  YWHAE is a possible susceptibility gene for schizophrenia that encodes 14-3-3epsilon, a Disrupted-in-Schizophrenia 1 (DISC1)-interacting molecule, but the effect of variation in its genotype on brain morphology remains largely unknown.
  
  
  METHODS
  In this voxel-based morphometric magnetic resonance imaging study, we conducted whole-brain analyses regarding the effects of YWHAE single-nucleotide polymorphisms (SNPs) (rs28365859, rs11655548, and rs9393) and DISC1 SNP (rs821616) on gray matter volume in a Japanese sample of 72 schizophrenia patients and 86 healthy controls. On the basis of a previous animal study, we also examined the effect of rs28365859 genotype specifically on hippocampal volume.
  
  
  RESULTS
  Whole-brain analyses showed no significant genotype effect of these SNPs on gray matter volume in all subjects, but we found significant genotype-by-diagnosis interaction for rs28365859 in the left insula and right putamen. The protective C allele carriers of rs28365859 had a significantly larger left insula than the G homozygotes only for schizophrenia patients, while the controls with G allele homozygosity had a significantly larger right putamen than the C allele carriers. The C allele carriers had a larger right hippocampus than the G allele homozygotes in schizophrenia patients, but not in healthy controls. No significant interaction was found between rs28365859 and DISC1 SNP on gray matter volume.
  
  
  CONCLUSIONS
  These different effects of the YWHAE (rs28365859) genotype on brain morphology in schizophrenia and healthy controls suggest that variation in its genotype might be, at least partly, related to the abnormal neurodevelopment, including in the limbic regions, reported in schizophrenia. Our results also suggest its specific role among YWHAE SNPs in the pathophysiology of schizophrenia.
authors.affiliation: Department of Neuropsychiatry, University of Toyama, Toyama, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Kido
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Neuropsychiatry, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nemoto
authors.affiliation: Department of Neuropsychiatry, University of Toyama, Toyama, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Branko
authors.initials: B
authors.lastname: Aleksic
authors.affiliation: Department of Neuropsychiatry, University of Toyama, Toyama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Furuichi
authors.affiliation: Department of Neuropsychiatry, University of Toyama, Toyama, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Radiology, University of Toyama, Toyama, Japan.
authors.forename: Kyo
authors.initials: K
authors.lastname: Noguchi
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo, Japan.
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.affiliation: Department of Neuropsychiatry, University of Toyama, Toyama, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics*; D000328:Adult; D000704:Analysis of Variance; D005260:Female; D005838:Genotype; D066128:Gray Matter / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*
chemical_list: D048948:14-3-3 Proteins; C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; C482983:YWHAE protein, human
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