Transcriptome-wide association study reveals two genes that influence mismatch negativity
Open accessAbstract
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.
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MMN is widely considered a robust marker of psychosis, thought to reflect an attempt to minimize prediction error and capture its disruption.
“MMN is widely considered to be a robust marker of psychosis15, thought to reflect an attempt to minimize this prediction error and capture its disruption16–19.”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [15]
The authors recently demonstrated reduced visual MMN responses in PD-VH, paralleling auditory MMN impairments observed in psychosis.
“We recently demonstrated reduced visual MMN responses in PD-VH20, paralleling auditory MMN impairments observed in psychosis15.”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [15]
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- Authors
- Bhat, A., Irizar, H., Thygesen, J. H., Kuchenbaecker, K., Pain, O., Adams, R. A., Zartaloudi, E., Harju-Seppänen, J., Austin-Zimmerman, I., Wang, B., Muir, R., Summerfelt, A., Du, X. M., Bruce, H., O’Donnell, P., Srivastava, D. P., Friston, K., Hong, L. E., Hall, M.-H., & Bramon, E.
- Affiliations
- Wellcome Centre for Human Neuroimaging (GB)
- University College London (GB)
- King's College London (GB)
- University of Maryland, Baltimore (US)
- Harvard University (US)
- Corresponding author
- Bhat, Anjali
- Bramon, Elvira
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 34
- Issue
- 11
- Pages
- 108868
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC7972991
- OpenAlex
- W3136028441
- Cited by
- 17
- References
- 86
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 1
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- SSRN Electronic Journal (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- Horizon 2020 Framework Programme
- Schizophrenia Research Fund
- UCLH Biomedical Research Centre (D79/543369/D-OTH/170890)
- South London and Maudsley NHS Foundation Trust
- Wellcome Trust (085475/Z/08/Z, 085475/B/08/Z)
- National Cancer Institute
- National Institute on Drug Abuse
- Korea Health Industry Development Institute (MC_PC_16014)
- National Heart, Lung, and Blood Institute
- National Institute for Health Research (NIHR200756, PDA/02/06/016)
- Harvard University
- National Human Genome Research Institute
- Mental Health Research UK
- Medical Research Council (D79/543369/D-OTH/170890, G0901310, G1100583)
- National Institute of Mental Health (R01MH116948, R01MH109687, R01MH112180)
- National Institute of Neurological Disorders and Stroke
- Horizon 2020 (747429)
- Pfizer
- Psychiatry Research Trust
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- mismatch negativity, transcriptome-wide association study, cortical gene expression, frontal cortex, lateral ventricular volume, auditory verbal learning, sensory processing
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Cerebral Ventricles, Child, Female, Humans, Male, Memory, Short-Term, Middle Aged, Phenotype, Receptors, Virus, Schizophrenia, Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase, Neurotransmitter Agents, Intracellular Signaling Peptides and Proteins, Genome-Wide Association Study, Electrophysiological Phenomena, Young Adult, Transcriptome, Intrinsically Disordered Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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