An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain☆

ZNF804A, a genomewide supported susceptibility gene for schizophrenia and bipolar disorder, has been associated with task-independent functional connectivity between the left and right dorsolateral prefrontal cortices. Several lines of evidence have converged on the hypothesis that this effect may b...

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Main Authors:	Sprooten, Emma, McIntosh, Andrew M., Lawrie, Stephen M., Hall, Jeremy, Sussmann, Jess E., Dahmen, Norbert, Konrad, Andreas, Bastin, Mark E., Winterer, Georg
Format:	Online
Language:	English
Published:	Elsevier 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778890/

id	pubmed-3778890
recordtype	oai_dc
spelling	pubmed-37788902013-09-23 An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain☆ Sprooten, Emma McIntosh, Andrew M. Lawrie, Stephen M. Hall, Jeremy Sussmann, Jess E. Dahmen, Norbert Konrad, Andreas Bastin, Mark E. Winterer, Georg Original Contribution ZNF804A, a genomewide supported susceptibility gene for schizophrenia and bipolar disorder, has been associated with task-independent functional connectivity between the left and right dorsolateral prefrontal cortices. Several lines of evidence have converged on the hypothesis that this effect may be mediated by structural connectivity. We tested this hypothesis using diffusion tensor magnetic resonance imaging in three samples: one German sample of 50 healthy individuals, one Scottish sample of 83 healthy individuals and one Scottish sample of 84 unaffected relatives of bipolar patients. Voxel-based analysis and tract-based spatial statistics did not detect any fractional anisotropy (FA) differences between minor allele carriers and individuals homozygous for the major allele at rs1344706. Similarly, region-of-interest analyses and quantitative tractography of the genu of the corpus callosum revealed no significant FA differences between the genotype groups. Examination of effect sizes and confidence intervals indicated that this negative finding is very unlikely to be due to a lack of statistical power. In summary, despite using various analysis techniques in three different samples, our results were strikingly and consistently negative. These data therefore suggest that it is unlikely that the effects of genetic variation at rs1344706 on functional connectivity are mediated by structural integrity differences in large, long-range white matter fiber connections. Elsevier 2012-12 /pmc/articles/PMC3778890/ /pubmed/22840435 http://dx.doi.org/10.1016/j.mri.2012.05.013 Text en © 2012 Elsevier Inc. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Sprooten, Emma McIntosh, Andrew M. Lawrie, Stephen M. Hall, Jeremy Sussmann, Jess E. Dahmen, Norbert Konrad, Andreas Bastin, Mark E. Winterer, Georg
spellingShingle	Sprooten, Emma McIntosh, Andrew M. Lawrie, Stephen M. Hall, Jeremy Sussmann, Jess E. Dahmen, Norbert Konrad, Andreas Bastin, Mark E. Winterer, Georg An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain☆
author_facet	Sprooten, Emma McIntosh, Andrew M. Lawrie, Stephen M. Hall, Jeremy Sussmann, Jess E. Dahmen, Norbert Konrad, Andreas Bastin, Mark E. Winterer, Georg
author_sort	Sprooten, Emma
title	An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain☆
title_short	An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain☆
title_full	An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain☆
title_fullStr	An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain☆
title_full_unstemmed	An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain☆
title_sort	investigation of a genomewide supported psychosis variant in znf804a and white matter integrity in the human brain☆
description	ZNF804A, a genomewide supported susceptibility gene for schizophrenia and bipolar disorder, has been associated with task-independent functional connectivity between the left and right dorsolateral prefrontal cortices. Several lines of evidence have converged on the hypothesis that this effect may be mediated by structural connectivity. We tested this hypothesis using diffusion tensor magnetic resonance imaging in three samples: one German sample of 50 healthy individuals, one Scottish sample of 83 healthy individuals and one Scottish sample of 84 unaffected relatives of bipolar patients. Voxel-based analysis and tract-based spatial statistics did not detect any fractional anisotropy (FA) differences between minor allele carriers and individuals homozygous for the major allele at rs1344706. Similarly, region-of-interest analyses and quantitative tractography of the genu of the corpus callosum revealed no significant FA differences between the genotype groups. Examination of effect sizes and confidence intervals indicated that this negative finding is very unlikely to be due to a lack of statistical power. In summary, despite using various analysis techniques in three different samples, our results were strikingly and consistently negative. These data therefore suggest that it is unlikely that the effects of genetic variation at rs1344706 on functional connectivity are mediated by structural integrity differences in large, long-range white matter fiber connections.
publisher	Elsevier
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778890/
_version_	1612013217657126912

An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain☆

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