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

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

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Article number108868
JournalCell Reports
Volume34
Issue number11
DOIs
Publication statusPublished - 16 Mar 2021

Keywords

  • Bayesian brain
  • endophenotype
  • gene expression
  • mismatch negativity
  • MMN
  • neurodevelopment
  • prediction error
  • psychosis
  • schizophrenia
  • transcriptome-wide association study

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