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

Mar 18, 2021

Contributor: Anjali Bhat,Haritz Irizar,Johan Hilge Thygesen,Karoline Kuchenbaecker,Oliver Pain,Rick A Adams,Eirini Zartaloudi,Jasmine Harju-Seppänen,Isabelle Austin-Zimmerman,Baihan Wang,Rebecca Muir,Ann Summerfelt,Xiaoming Michael Du,Heather Bruce,Patricio O'Donnell,Deepak P Srivastava,Karl Friston,L Elliot Hong,Mei-Hua Hall,Elvira Bramon

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

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.
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

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Anjali Bhat

Division of Psychiatry, University College London, London, UK; Wellcome Centre for Human Neuroimaging, University College London, London, UK; Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK; MRC Centre for Neurodevelopmental Disorders, King’s College London, London, UK. Electronic address: anjali.bhat.14@ucl.ac.uk.

Haritz Irizar

Division of Psychiatry, University College London, London, UK.

Johan Hilge Thygesen

Division of Psychiatry, University College London, London, UK.

Karoline Kuchenbaecker

Division of Psychiatry, University College London, London, UK; UCL Genetics Institute, University College London, London, UK.

Oliver Pain

Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK.

Rick A Adams

Division of Psychiatry, University College London, London, UK; Institute of Cognitive Neuroscience, University College London, London, UK.

Eirini Zartaloudi

Division of Psychiatry, University College London, London, UK.

Jasmine Harju-Seppänen

Division of Psychiatry, University College London, London, UK; Department of Clinical, Educational and Health Psychology, University College London, London, UK.

Isabelle Austin-Zimmerman

Division of Psychiatry, University College London, London, UK.

Baihan Wang

Division of Psychiatry, University College London, London, UK.

Rebecca Muir

Division of Psychiatry, University College London, London, UK.

Ann Summerfelt

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland, Baltimore, MD, USA.

Xiaoming Michael Du

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland, Baltimore, MD, USA.

Heather Bruce

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland, Baltimore, MD, USA.

Patricio O’Donnell

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland, Baltimore, MD, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Takeda Pharmaceuticals, Cambridge, MA, USA.

Deepak P Srivastava

Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK; MRC Centre for Neurodevelopmental Disorders, King’s College London, London, UK.

Karl Friston

Wellcome Centre for Human Neuroimaging, University College London, London, UK.

L Elliot Hong

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland, Baltimore, MD, USA.

Mei-Hua Hall

Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Psychosis Neurobiology Laboratory, McLean Hospital, Belmont, MA, USA.

Elvira Bramon

Division of Psychiatry, University College London, London, UK; Institute of Cognitive Neuroscience, University College London, London, UK; Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK; Camden and Islington NHS Foundation Trust, London, UK. Electronic address: e.bramon@ucl.ac.uk.

References

PubMed