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The impact of psychosis genome-wide associated ZNF804A variation on verbal fluency connectivity

Tecelão, D; Mendes, A; Martins, D; Bramon, E; Toulopoulou, T; Kravariti, E; Murray, R; (2017) The impact of psychosis genome-wide associated ZNF804A variation on verbal fluency connectivity. Journal of Psychiatric Research , 98 pp. 17-21. 10.1016/j.jpsychires.2017.12.005. Green open access

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Schizophrenia (SCZ) and bipolar disorder (BD) have high heritability. Genome-wide association studies (GWAS) have identified ZNF804A as a significant risk gene for both illnesses. A validation of this finding at the brain systems-level is imperative as there is still little understanding of how it heightens risk. Based in part on our recent findings of an effect on widespread decreased white matter microstructural fractional anisotropy (putatively a proxy of its integrity), particularly strong in SCZ, we asked whether the risk allele has a detrimental effect on regional brain activation and functional connectivity during a type of cognitive processing which is, together with its neural correlates, impaired in BD and SCZ: verbal fluency. Functional MRI and genotype data was collected from 80 healthy volunteers, and 54 SCZ and 40 BD patients. A standard multifactorial analysis of variance using statistical parametric mapping and significance correction of FWE p < 0.05 was used. We found the GWAS risk allele A was associated with decreased positive functional coupling between the left precentral gyrus/inferior frontal gyrus (i.e. the most highly recruited area for the task) and: 1) the left inferior frontal gyrus, and 2) the left posterior cingulate gyrus, encompassing the precuneus; both as a main effect across controls and psychosis patients. Such association of the risk allele with reduced functional connectivity (with no area where the opposite main effect was detected), converges with findings in other tasks, our previous finding of its widespread impact on brain white matter microstructure, and with the dysconnectivity hypothesis of SCZ.

Type: Article
Title: The impact of psychosis genome-wide associated ZNF804A variation on verbal fluency connectivity
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jpsychires.2017.12.005
Publisher version: http://doi.org/10.1016/j.jpsychires.2017.12.005
Language: English
Additional information: Copyright © 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
Keywords: Bipolar disorder, Genome-wide association, Neuroimaging genetics, Psychosis, Schizophrenia, ZNF804A
URI: http://discovery.ucl.ac.uk/id/eprint/10041286
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