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

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 - PLoS ONE (2014)

Bottom Line: 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.No significant interaction was found between rs28365859 and DISC1 SNP on gray matter volume.Our results also suggest its specific role among YWHAE SNPs in the pathophysiology of schizophrenia.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuropsychiatry, University of Toyama, Toyama, Japan.

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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Related in: MedlinePlus

The YWHAE (rs28365859) genotype-by-diagnosis interaction on gray matter volume.The regions showing interaction in all subjects are displayed by a hot colormap. The color bar shows t values corresponding to the color in the figure.
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pone-0103571-g001: The YWHAE (rs28365859) genotype-by-diagnosis interaction on gray matter volume.The regions showing interaction in all subjects are displayed by a hot colormap. The color bar shows t values corresponding to the color in the figure.

Mentions: There was no significant genotype effect of YWHAE SNPs or rs821616 on GM volume in all subjects. However, we found significant genotype-by-diagnosis interactions for rs28365859 in the left insula and right putamen GM volume (uncorrected p<0.0001, extent threshold k>50; Table 2 and Fig. 1), which were confirmed by subsequent FWE-corrected SVC analyses (left insula, p = 0.004; right putamen, p = 0.001) (Table 2). Other SNPs (rs11655548, rs9393, and rs821616) had no genotype-by-diagnosis interaction. There was no significant gene-gene interaction on GM volume between rs28365859 and rs821616.


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

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 - PLoS ONE (2014)

The YWHAE (rs28365859) genotype-by-diagnosis interaction on gray matter volume.The regions showing interaction in all subjects are displayed by a hot colormap. The color bar shows t values corresponding to the color in the figure.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126687&req=5

pone-0103571-g001: The YWHAE (rs28365859) genotype-by-diagnosis interaction on gray matter volume.The regions showing interaction in all subjects are displayed by a hot colormap. The color bar shows t values corresponding to the color in the figure.
Mentions: There was no significant genotype effect of YWHAE SNPs or rs821616 on GM volume in all subjects. However, we found significant genotype-by-diagnosis interactions for rs28365859 in the left insula and right putamen GM volume (uncorrected p<0.0001, extent threshold k>50; Table 2 and Fig. 1), which were confirmed by subsequent FWE-corrected SVC analyses (left insula, p = 0.004; right putamen, p = 0.001) (Table 2). Other SNPs (rs11655548, rs9393, and rs821616) had no genotype-by-diagnosis interaction. There was no significant gene-gene interaction on GM volume between rs28365859 and rs821616.

Bottom Line: 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.No significant interaction was found between rs28365859 and DISC1 SNP on gray matter volume.Our results also suggest its specific role among YWHAE SNPs in the pathophysiology of schizophrenia.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuropsychiatry, University of Toyama, Toyama, Japan.

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.

Show MeSH
Related in: MedlinePlus