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Transcriptome-wide association study reveals two genes that influence mismatch negativity.

Bhat, A; Irizar, H; Thygesen, JH; Kuchenbaecker, K; Pain, O; Adams, RA; Zartaloudi, E; ... Bramon, E; + view all (2021) Transcriptome-wide association study reveals two genes that influence mismatch negativity. Cell Reports , 34 (11) , Article 108868. 10.1016/j.celrep.2021.108868. Green open access

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Abstract

Mismatch negativity (MMN) is a differential electrophysiological response measuring cortical adaptability to unpredictable stimuli. MMN is consistently attenuated in patients with psychosis. However, the genetics of MMN are uncharted, limiting the validation of MMN as a psychosis endophenotype. Here, we perform a transcriptome-wide association study of 728 individuals, which reveals 2 genes (FAM89A and ENGASE) whose expression in cortical tissues is associated with MMN. Enrichment analyses of neurodevelopmental expression signatures show that genes associated with MMN tend to be overexpressed in the frontal cortex during prenatal development but are significantly downregulated in adulthood. Endophenotype ranking value calculations comparing MMN and three other candidate psychosis endophenotypes (lateral ventricular volume and two auditory-verbal learning measures) find MMN to be considerably superior. These results yield promising insights into sensory processing in the cortex and endorse the notion of MMN as a psychosis endophenotype.

Type: Article
Title: Transcriptome-wide association study reveals two genes that influence mismatch negativity.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2021.108868
Publisher version: https://doi.org/10.1016/j.celrep.2021.108868
Language: English
Additional information: © 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: Bayesian brain, MMN, endophenotype, gene expression, mismatch negativity, neurodevelopment, prediction error, psychosis, schizophrenia, transcriptome-wide association study
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > Comprehensive CTU at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10124937
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