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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

Impact of the rs28365859 genotype on gray matter volume of the right hippocampus in schizophrenia.Age, sex, illness duration, and medication dose were used as covariates. The protective C allele carriers had a significantly larger right hippocampus than the G allele homozygotes. Anatomical localizations are displayed on the normal template MR images in three directions. The color bar shows t values corresponding to the color in the figure.
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pone-0103571-g004: Impact of the rs28365859 genotype on gray matter volume of the right hippocampus in schizophrenia.Age, sex, illness duration, and medication dose were used as covariates. The protective C allele carriers had a significantly larger right hippocampus than the G allele homozygotes. Anatomical localizations are displayed on the normal template MR images in three directions. The color bar shows t values corresponding to the color in the figure.

Mentions: The protective C allele carriers of rs28365859 had a significantly larger right, but not left, hippocampal volume than the G allele homozygotes (FWE-corrected p = 0.009, Table 3). For the analyses in each diagnostic group, such an effect of YWHAE genotype was significant only in schizophrenia patients (FWE-corrected p = 0.009, Table 3 and Fig. 4). That result in schizophrenia remained the same even when we added illness duration and medication as covariates (Table 3).


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)

Impact of the rs28365859 genotype on gray matter volume of the right hippocampus in schizophrenia.Age, sex, illness duration, and medication dose were used as covariates. The protective C allele carriers had a significantly larger right hippocampus than the G allele homozygotes. Anatomical localizations are displayed on the normal template MR images in three directions. 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-g004: Impact of the rs28365859 genotype on gray matter volume of the right hippocampus in schizophrenia.Age, sex, illness duration, and medication dose were used as covariates. The protective C allele carriers had a significantly larger right hippocampus than the G allele homozygotes. Anatomical localizations are displayed on the normal template MR images in three directions. The color bar shows t values corresponding to the color in the figure.
Mentions: The protective C allele carriers of rs28365859 had a significantly larger right, but not left, hippocampal volume than the G allele homozygotes (FWE-corrected p = 0.009, Table 3). For the analyses in each diagnostic group, such an effect of YWHAE genotype was significant only in schizophrenia patients (FWE-corrected p = 0.009, Table 3 and Fig. 4). That result in schizophrenia remained the same even when we added illness duration and medication as covariates (Table 3).

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