The polymorphism of YWHAE, a gene encoding 14-3-3epsilon, and brain morphology in schizophrenia: A voxel-based morphometric study

Mikio Kido, Yukako Nakamura, Kiyotaka Nemoto, Tsutomu Takahashi, Branko Aleksic, Atsushi Furuichi, Yumiko Nakamura, Masashi Ikeda, Kyo Noguchi, Kozo Kaibuchi, Nakao Iwata, Norio Ozaki, Michio Suzuki

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Article numbere103571
JournalPloS one
Volume9
Issue number8
DOIs
Publication statusPublished - 08-08-2014

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Gene encoding
Polymorphism
Brain
Schizophrenia
Nucleotides
genetic polymorphism
brain
single nucleotide polymorphism
Genes
Single Nucleotide Polymorphism
Genotype
genes
Alleles
genotype
alleles
homozygosity
Putamen
Homozygote
Magnetic resonance
Animals

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Kido, M., Nakamura, Y., Nemoto, K., Takahashi, T., Aleksic, B., Furuichi, A., ... Suzuki, M. (2014). The polymorphism of YWHAE, a gene encoding 14-3-3epsilon, and brain morphology in schizophrenia: A voxel-based morphometric study. PloS one, 9(8), [e103571]. https://doi.org/10.1371/journal.pone.0103571
Kido, Mikio ; Nakamura, Yukako ; Nemoto, Kiyotaka ; Takahashi, Tsutomu ; Aleksic, Branko ; Furuichi, Atsushi ; Nakamura, Yumiko ; Ikeda, Masashi ; Noguchi, Kyo ; Kaibuchi, Kozo ; Iwata, Nakao ; Ozaki, Norio ; Suzuki, Michio. / The polymorphism of YWHAE, a gene encoding 14-3-3epsilon, and brain morphology in schizophrenia : A voxel-based morphometric study. In: PloS one. 2014 ; Vol. 9, No. 8.
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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.",
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Kido, M, Nakamura, Y, Nemoto, K, Takahashi, T, Aleksic, B, Furuichi, A, Nakamura, Y, Ikeda, M, Noguchi, K, Kaibuchi, K, Iwata, N, Ozaki, N & Suzuki, M 2014, 'The polymorphism of YWHAE, a gene encoding 14-3-3epsilon, and brain morphology in schizophrenia: A voxel-based morphometric study', PloS one, vol. 9, no. 8, e103571. https://doi.org/10.1371/journal.pone.0103571

The polymorphism of YWHAE, a gene encoding 14-3-3epsilon, and brain morphology in schizophrenia : A voxel-based morphometric study. / Kido, Mikio; Nakamura, Yukako; Nemoto, Kiyotaka; Takahashi, Tsutomu; Aleksic, Branko; Furuichi, Atsushi; Nakamura, Yumiko; Ikeda, Masashi; Noguchi, Kyo; Kaibuchi, Kozo; Iwata, Nakao; Ozaki, Norio; Suzuki, Michio.

In: PloS one, Vol. 9, No. 8, e103571, 08.08.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The polymorphism of YWHAE, a gene encoding 14-3-3epsilon, and brain morphology in schizophrenia

T2 - A voxel-based morphometric study

AU - Kido, Mikio

AU - Nakamura, Yukako

AU - Nemoto, Kiyotaka

AU - Takahashi, Tsutomu

AU - Aleksic, Branko

AU - Furuichi, Atsushi

AU - Nakamura, Yumiko

AU - Ikeda, Masashi

AU - Noguchi, Kyo

AU - Kaibuchi, Kozo

AU - Iwata, Nakao

AU - Ozaki, Norio

AU - Suzuki, Michio

PY - 2014/8/8

Y1 - 2014/8/8

N2 - 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.

AB - 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.

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