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ZNF804A genetic variation (rs1344706) affects brain grey but not white matter in schizophrenia and healthy subjects

Published online by Cambridge University Press:  20 May 2014

I. Nenadic*
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
R. Maitra
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
F. B. Basmanav
Affiliation:
Institute of Human Genetics, University of Bonn, Bonn, Germany
C. C. Schultz
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
C. Lorenz
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
C. Schachtzabel
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
S. Smesny
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
M. M. Nöthen
Affiliation:
Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
S. Cichon
Affiliation:
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, Germany Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland
J. R. Reichenbach
Affiliation:
Medical Physics Group, Institute for Diagnostic and Interventional Radiology I (IDIR I), Jena University Hospital, Germany
H. Sauer
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
R. G. M. Schlösser
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
C. Gaser
Affiliation:
Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany Department of Neurology, Jena University Hospital, Jena, Germany
*
*Address for correspondence: I. Nenadic, M.D., Department of Psychiatry and Psychotherapy, Jena University Hospital, Philosophenweg 3, 07743 Jena, Germany. (Email: igor.nenadic@uni-jena.de)

Abstract

Background

Genetic variation in the gene encoding ZNF804A, a risk gene for schizophrenia, has been shown to affect brain functional endophenotypes of the disorder, while studies of white matter structure have been inconclusive.

Method

We analysed effects of ZNF804A single nucleotide polymorphism rs1344706 on grey and white matter using voxel-based morphometry (VBM) in high-resolution T1-weighted magnetic resonance imaging scans of 62 schizophrenia patients and 54 matched healthy controls.

Results

We found a significant (p < 0.05, family-wise error corrected for multiple comparisons) interaction effect of diagnostic group x genotype for local grey matter in the left orbitofrontal and right and left lateral temporal cortices, where patients and controls showed diverging effects of genotype. Analysing the groups separately (at p < 0.001, uncorrected), variation in rs1344706 showed effects on brain structure within the schizophrenia patients in several areas including the left and right inferior temporal, right supramarginal/superior temporal, right and left inferior frontal, left frontopolar, right and left dorsolateral/ventrolateral prefrontal cortices, and the right thalamus, as well as effects within the healthy controls in left lateral temporal, right anterior insula and left orbitofrontal cortical areas. We did not find effects of genotype of regional white matter in either of the two cohorts.

Conclusions

Our findings demonstrate effects of ZNF804A genetic variation on brain structure, with diverging regional effects in schizophrenia patients and healthy controls in frontal and temporal brain areas. These effects, however, might be dependent on the impact of other (genetic or non-genetic) disease factors.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2014 

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